WO2000040210A2

WO2000040210A2 - Topical compositions comprising protected functional thiols

Info

Publication number: WO2000040210A2
Application number: PCT/US2000/000444
Authority: WO
Inventors: Robert Wayne Glenn, Jr.; Alan Roy Katritzky; Eric Block; Matthew David Shair; Matthew David Butts
Original assignee: The Procter & Gamble Company; General Electric Company
Priority date: 1999-01-08
Filing date: 2000-01-07
Publication date: 2000-07-13
Also published as: AU2603700A; CA2356325A1; WO2000040210A3; CN1433297A; BR0007437A; US6544499B1; JP2002541058A; EP1143916A2; CA2356325C

Abstract

This invention relates to a topical composition for treating amino acid based substrates comprising a protected thiol compound having the formula R—(S—Pr)m where R is a functional group, S is sulfur, and Pr is a heterocyclic protecting group, and m is an integer between 1 and 100. The invention further relates to systems which comprise this protected thiol compound and an activating mechanism. The protected thiol compounds of the present invention may be used in hair care compositions, textile care compositions, cosmetic compositions, oral care compositions, skin care, nail care, laundry care, acne care and animal care compositions. A preferred embodiment of the present invention provides a silicone composition and method for making. The composition comprises a polysiloxane or silicone resin, at least one linker, and at least one molecular hook.

Description

TOPICAL COMPOSITIONS COMPRISING PROTECTED FUNCTIONAL THIOLS

TECHNICAL FIELD

The present invention relates to topical compositions for treating amino acid based substrates. The topical compositions comprise cosmetic or therapeutic actives that have been bound to a protected thiol which acts as a molecular 'hook' to impart "permanent" benefits to the ammo acid based substrates. The ammo acid based substrates can include, for example, protemaceous mateπals such as keratm, as found in human hair, animal fur, velus hair on skm, finger and toe nails; vanous animal body parts, such as horns, hooves and feathers; other naturally occurring protein containing mateπals, such as wool; and synthetic polymers. Of particular interest are compositions which deliver and attach cosmetic actives to human hair.

BACKGROUND OF THE INVENTION

It is well known in the art that ammo-acid based fibers, particularly hair, can be treated with agents that deliver one or more cosmetic benefits, such as conditioning, styling or setting. The conventional cosmetic products which have been known and used commercially have relied upon two key factors: deposition and retention. The cosmetic actives must first be physically deposited onto the hair fiber where the active imparts a benefit to a sufficient degree. Secondly, it is essential that the cosmetic actives be retained on the hair beyond the completion of the treatment. For example, when hair is πnsed to remove unwanted excess composition (e.g., a conditioner) a sufficient amount of the cosmetic active (humectant, moistuπzer, etc.) remains bonded to the hair so as to maintain the desired cosmetic benefits.

The bonding of the cosmetic active mateπal to the hair is generally of the nature of physico-chemical mtermolecular forces, e.g., physisorption. Such physical forces compπse, for example, hydrogen bonding, electrostatic interactions, van der Waals interactions and the like. As an example, cationic cosmetic agents, generally of the quaternary ammonium type, are known to bond to hair by virtue of the interaction of their cations with anionic ammo acid residues within keratin, e.g., glutamic acid, aspartic acid, cysteic acid etc. A major problem, however, with physisorption is the inevitable short lived retention of the cosmetic agent on hair. This is due to the relatively weak physical forces which bind the cosmetic to hair and which are easily disrupted by other treatments, e g washing And, given the frequent need for treating hair, performance retention is difficult to achieve and generally does not last in excess of the period between washes.

One approach that has been disclosed in the art to overcome the above problem to provide truly durable or "permanent" cosmetic benefits to hair that are retained through multiple washes is to utilize molecular "hooks" to chemically bond cosmetic actives to hair keratin, e.g., chemisorption. Chemisorption results in a permanent juncture that is essentially resistant to physical wear from subsequent washings or physical abrasion. Two conventional approaches to achieve chemisorption compπse the use of either electrophihc reactive moieties or thiol reactive moieties attached to the cosmetic active. Electrophihc reactive moieties are designed to react with thiol functional groups present m hair and thiol reactive moieties are designed to react with electrophihc functional groups within the hair to create a covalent bond.

U.S. Patent 5,523,080 issued to Gough et al. on June 4, 1996, U.S. Patent 5,211,942 issued to Deppert et al. on May 18, 1993, and UK Patent Application GB2197887 published on June 2, 1988, all disclose the use of electrophihc moieties. These electrophihc chemistπes include the use of azlactone, (haloalkyl)tπalkylammonιum salts, and acyl hahdes. All of these molecular hooks have potential to react with hair via an electrophihc mechanism which necessitates sufficient nucleophihc functional groups present within the keratm structure with which to react to a sufficient degree to achieve the desired durable benefits. For hair, this poses a dilemma in that it is generally known that hair does not naturally possess a sufficient concentration of nucleophihc functional groups under consumer mild conditions to dπve the reaction. However, it is also generally known that by chemically reducing the disulfide bonds present with the cystine ammo acid residues of hair, in a manner analogous to cold waving, sufficient quantities of nucleophihc cystine residues can be produced. Pre-reduction of hair, to enable the chemical reaction with suitable electrophihc cosmetic actives, is illustrated below in reactions (a) and (b). Ker represents keratm protein, R-X represents an alkyl halide electrophihc cosmetic active, R represents a cosmetic agent and X^" is a halide anion such as bromide or chloπde.

Reduction

Ker S S Ker »- 2 Ker SH

(a) Ker SH + R X *~ Ker S R + X^"

While electrophihc cosmetic actives have been demonstrated effective at providing durable cosmetic benefits to hair, the approach has disadvantages that arise from the required pre- reduction step First, the reduction step is known to be a very harsh chemical process that imparts considerable damage to hair Second, the effective reducing agents are typically mercaptans of low molecular weight and are odiferous. The pre-reduction process generates unpleasant malodor that remains on the hair for greater than a week time m most instances Thirdly, in addition to unpleasant malodor and resulting hair damage, the required pre-reduction imparts an additional step to the process with attendant added inconvenience to the user

U S Patent 5,087,733 and U S Patent 5,206,013 both issued to Deppert et al on February 11, 1992 and Apπl 27, 1993 respectively, as well as U S Patent 4,973,475 issued to Schnetzmger and Ciaudelh on November 27, 1990, descπbe the use of quaternary ammonium thiols which fall under the general class of nucleophihc reactive actives Such nucleophihc actives are generally intended to react with cystine ammo acid residues present within hair via formation of a mixed disulfide covalent linkage as is demonstrated in the chemical equation (c).

R— SH + Ker— S— S-Ker *~ Ker— S^~ S— R + Ker-SH (_c)

Ker represents keratm and R-SH represents a suitable nucleophihc active where R is a cosmetic agent and -SH representing a nucleophihc moiety. It is generally known that thiols are the preferred nucleophihc reactive moieties that possess enough reactive strength to chemically bond with the disulfide bond of cystine, Ker-S-S-Ker, under safe and mild consumer conditions (e.g , relatively non toxic, less than 120°F, pH 2 to 11). Most other prospective nucleophihc molecular handles are either highly toxic (e g , selenols), or are unreactive under mild conditions (e.g , alkoxides with pKa ~ 15).

There are two major drawbacks to the use of nucleophihc thiols as reactive moieties to form covalent bonds with keratm. First, thiol nucleophihc moieties are known to be unstable in the presence of air. Atmosphere induced oxidation of the thiols to the corresponding, and unreactive, disulfide as is shown in the following equation (d) where R-SH represents a suitable nucleophihc cosmetic active R being an alkyl cosmetic agent and -SH representing the nucleophihc moiety:

R-SH + R-SH °^{mSm >} R- S- S-R (d)

Such oxidative deactivation of the nucleophihc thiol moieties severely limits their mode of usage. Thus, nucleophihc thiols are generally not stable enough to be utilized as such m a large majoπty of current product forms, 1 e . re-sealable hair care packages widely used for shampoos, rmse-off conditioners etc Second, the nucleophihc thiol moiety has very little affinity for hair keratin and has very low aqueous solubility, both of which hinder its performance in generating durable cosmetic benefits, especially when attached to hydrophobic, insoluble cosmetic actives, 1 e , hydrocarbon conditioners, m-soluble polymers etc

Despite major efforts, however, the art has not yet provided molecular "hooks" that provide durable cosmetic benefits to hair that last beyond twenty shampoos and which do not necessitate the damaging cold waving of hair, 1 e. hair reduction, while being oxidatively stable in solution for long term storage m a variety of currently used product forms, e.g., πnse of conditioners, two- m-one shampoos, etc.

The present invention is concerned with topical compositions compnsing classes of compounds containing at least one thiol in a protected form, which can be released to provide a - SH or -S^" group pπor or simultaneous to use These protected thiols are referred to herein as "hooks" It is understood that withm the scope of this invention that functional thiols as represented herein include both the protonated thiol, R-SH, and unprotonated thiolate, R-S^"

It has now been discovered that, surpπsmgly, such "hooks", R-(S-Pr)_m, provide durable cosmetic benefits, when applied to ammo-acid based substrates without a damaging cold-waving process, that last beyond twenty shampoos. It has also been discovered that the molecular "hooks" of the present invention provide improved oxidative stability versus conventional thiols by virtue of the appended protecting moiety to the thiol group that reduces the oxidative susceptibility of the sulfur atom(s). Furthermore, it has been found that these molecular "hooks" significantly outperform conventional nucleophihc thiol hooks in providing durable cosmetic benefits. While not being bound by theory, the latter observed effect is believed to be due to the unexpected high affinity for keratm provided by certain polaπzable electrophihc groups which offer improved solubility and possibly even electrostatic interaction with the charged keratmaceous substrate. Presumably, such greater affinity affords enhanced diffusion and adsorption to the fiber by the cosmetic active enabling greater opportunity for binding.

The 'hooks' of the present invention enable the achievement of durable cosmetic benefits that are resistant to cleansing or shampooing from essentially a non-damagmg process that is void of cold waving. The binding of the cosmetic actives provided by these molecular 'hooks' is to such a degree of durability that the measured cosmetic benefits will remain in hair for multiple shampoo cycles, e.g. eight to twenty or more. While not being restricted by theory, it is believed that such a high degree of durability is due to the formation of covalent bonds between the cosmetic active and the keratmaceous substrate. This bond formation may occur in either of two ways. First, the protected thiol compound can be mixed with a activating release agent to form the free functional thiol, reaction (e) The free thiol will then react with the substrate thereby attaching the functional group, reaction (f).

R- S — Pr + Release Agent *^■ R— S^" (e)

2 R— s^" + Ker— S — S^~ Ker - 2 Ker — S— S — R -r Ker-SH (f)

R represents the cosmetic active, Ker represents the keratin protein, S represents sulfur, -SH represents the thiol and Pr represents the protecting group. Based on theory, the above thiol- protecting group bond is broken via some form of activation yielding the reactive unprotected thiol which would then be capable of forming a mixed disulfide with keratm disulfides via nucleophihc displacement. Such activation could be accomplished via hydrolysis or by the action of a nucleophile other than water, either m the substrate itself or in a separate composition Such hydrolysis or nucleophihc attack can itself be enhanced m several way such as by application of a source of energy or catalysis. This mixing may be done pπor to use or simultaneously, duπng application to the substrate. Where the mixing occurs simultaneously to application, the release of the protecting group occurs in-situ on the substrate.

Surpπsingly, it has been found that, alternatively, the formation of the covalent bonds may occur without mixing with a release agent. Direct reaction of certain protected thiol compounds with the hair occurs via the formation of a mixed disulfide with the existing disulfide bonds withm keratm as is illustrated below, reaction (g):

R-S— Pr + Ker-S— S— Ker -^ R-S— S-Ker + Ker- SH + Pr- OH fe) While not being bound to theory, it is believed that the keratin itself could be activating the thiol protecting group bond to enable the observed durable benefits. The resulting free protecting group may or may not undergo decomposition reactions. The byproducts of the activation of the sulfur-heterocychc bond will usually be removed from the substrate by washing.

The cosmetic agent, R, of the present invention may be monofunctionahzed, i.e. the cosmetic active moiety, R, carπes a single molecular "hook" connected to the cosmetic agent via a sulfur-sp³ carbon bond, or it may be bis- or multi- functionahzed, i.e. the cosmetic active, R, may carry two or more sp³ electrophiles connected to the cosmetic agent via separate sulfur-sp³ carbon bonds. The latter may be useful for example m achieving a greater degree of chemical bonding of the cosmetic agent to the substrate or for generating bonds between adjacent features of the substrate, e.g. producing a cross-lmkmg effect. The latter may be employed to improve the strength or tensile properties of keratmaceous fibers or for enhancing the degree of hair setting compared with pπor art hair methods. It is understood that within the scope of this invention, numerous potentially and actually tautomeπc compounds are involved. Thus, for example, 2-mercaptopyπdιne (I) exists under known conditions m the pyπdme-2-thιone tautomer form (II). It is to be understood that when this development refers to a particular structure, all of the reasonable additional tautomeπc structures are included. In the art, tautomeπc structures are frequently represented by one single structure and the present invention follows this general practice.

(I) (LT)

Preferred embodiments of the present invention are related to functional silicone compositions More specifically, these embodiments are related to functional silicone compositions which are used in the cosmetics industry.

Silicones are widely used in hair care products due to the conditioning benefit that they impart to hair. By modern day technology, the silicone is deposited on hair during the application process but is held only by weak physical forces, such as hydrogen bonding or van der Waals interactions. Because the forces are weak, the benefits of silicone by deposition are short lived. Beneficial conditioning effect can also be caused by treating hair with silanol capped ammo-functionahzed silicones. These can undergo condensation cure reactions on hair to form somewhat durable films. Generally, conditioning benefits are attributed to the deposition of high molecular weight, high viscosity fluids and gums which can weight down the hair.

It is widely known by those skilled in the art that covalent bonding is the key to "permanent" hair treatment. Processes which alter the structure of the hair, such as permanent wave and color treatment methods, do provide longer lasting effects. These processes include glycolate reduction and peroxide reoxidation. However, the processes are very damaging to hair and can only be earned out every eight to ten weeks.

Gough et al. in U.S. Patent Nos. 5,523,080 and 5,525,332 descnbe the synthesis of sihcone- azlactone polymers which exhibit covalent bonding and "permanent" conditioning benefit. Gough et al. discuss incorporating an azlactone-functionalized copolymer which consists of vmylazlactone and methacryloyl polydimethylsiloxane monomers into a sihcone-active group- hair structure. The hair treatment using the sihcone-azlactone polymers did not consist of the steps of reduction with a glycolate or reoxidation with peroxide.

New compositions are constantly being sought which impart improved hair care benefits without a harsh, damaging chemical treatment.

SUMMARY OF THE INVENTION

This invention relates to a topical composition for treating ammo acid based substrates compnsing a protected thiol compound having the formula

R-<S— Pr)_m where R is a mono or multivalent cosmetically active functional group, S is sulfur, and Pr is a protecting group, and m is an integer between 1 and 100. The invention further relates to systems which compπse this protected thiol compound and an activating mechanism. The protected thiol compounds of the present invention may be used in hair care compositions, textile care compositions, cosmetic compositions, oral care compositions, skin care, nail care, laundry care, acne care and animal care compositions

A preferred embodiment of the present invention provides a silicone composition and method for making. The composition compnses a polysiloxane or silicone resm, at least one linker, and at least one molecular hook.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to topical compositions which provide attachment of functional groups to ammo acid based substrates.

As used herein, "cystme containing, ammo acid based substrates" are proteinaceous mateπals which contain the amino acid cystine in its amino acid sequence. The phrase "amino acid sequence" refers to a specific configuration of the ammo acids comprising a protein. Cystine amino acid units are represented by Ker-S-S-Ker and cysteine amino acid units by Ker- SH. The compositions of the present invention can be used to attach functional groups to materials such as keratm, as found m human and animal hair, skm and nails; various animal body parts such as horns, hooves and feathers; and other naturally occurnng protein containing materials, such as wool.

The topical compositions of the present invention can compπse, consist of, or consist essentially of the essential elements and limitations of the invention descnbed herein, as well as any of the additional or optional ingredients, components, or limitations described herein.

All percentages, parts and ratios are by weight of the total composition, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the specific ingredient level and, therefore, do not include solvents, earners, by-products, filler or other minor ingredients that may be included in commercially available matenals, unless otherwise specified.

PROTECTED THIOL COMPOUND

The compositions of the present invention compπse a protected thiol compound having the formula

R_<S— Pr)_m where R is a mono or multivalent cosmetically active functional group, S is sulfur, Pr is a protecting group, and m is an integer ranging from about 1 to about 100, preferably from about 1 to about 50, more preferably equal to 1 to about 20, and most preferably equal to 1 to about 5.

Typically, the protected thiol compounds of the present invention are present m the compositions of the invention in an amount from about 0.000001% to about 30%, preferably from about 0 0001% to about 25%, more preferably from 0 01 to about 20%, even more preferably from about 0 1% to about 10%, and most preferably from about 1% to about 5%, by weight of the composition Suitable ranges of amounts will generally depend upon the functional group in question For example, hair conditioners that are modified with the molecular hooks' of the present invention will normally be present from about 0 01% to 10% by weight of the composition, and hair styling agents that are modified such as cationic conditioning polymers or polyisobutylene will normally be present from about 0 01 to 10% by weight of the composition, perfluoropolyether mateπals that are modified may be present from about 0 000001 to 0 1% by weight of the composition, hair dye chromophonc matenals may be present from 0 1% to 10% and other film forming polymers that are modified may be present from about 0 01 to 2% of the composition

The protected thiol compound compnses from about 1 to about 100, preferably from about 1 to about 50, more preferably from about 1 to 20, and most preferably equal from 1 to about 5 sulfur atoms, each linked to one protective group Protecting Group

The protected thiol compounds of the present invention compnse 1 to about 100, preferably 1 to 50, more preferably 1 to 20 and most preferably 1 to 5 protecting groups The protecting group may be selected from the range consisting of heterocyclic protecting groups, sp² aliphatic trigonal carbon protecting groups, sp³ carbon protecting groups, metal based protecting groups, non-metal and metalloid based protecting groups, energy-sensitive protecting groups and mixtures thereof The protecting group is preferably selected from the range consisting of heterocyclic protecting groups, sp² aliphatic tngonal carbon protecting groups, sp³ carbon protecting groups and non-metal protecting groups The protecting group is more preferably selected from heterocyclic protecting groups, sp² aliphatic tngonal carbon protecting groups and non-metal protecting groups

Heterocyclic Protecting Groups - The cosmetic composition of the present invention comprises a protected thiol compound wherein the thiol protective group may be a heterocyclic nng or ring system Heterocyclic groups that are suitable for use m the present invention include mono- or polyunsaturated or saturated heterocyclic nngs, heterocyclic nng systems, fused heterocyclic ring systems, substituted heterocyclic nngs, substituted heterocyclic nng systems or substituted fused heterocyclic nng systems The heterocyclic nngs contain from about three to about thirty members, and may contain electronegative heteroatoms including N, O, S, or P The heterocyclic nngs or nng systems also may contain exocyclic double bonds of the C=M type wherein M is O, S, NA¹ or CA'A² A¹ and A² used here, and A³ and A⁴ used hereinafter, each represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or polycychc aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroahphatic or heteroolefmic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or perfluoro substitution.

Optional substituents on the heterocyclic nng or ring system, X¹, X², X³, X⁴ X⁵..., can be selected from electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between -1.0 and +1.5 which can be non-ionic, zwitteriomc, cationic or anionic comprising for example C-lmked groups of the classes defined above as A¹, A², A³, and A⁴; S- hnked groups including SA¹, SCN, SO₂A\ SO₃A¹, SSA¹, SOA¹, SOzNA'A², SNA¹ A², S(NA')A², S(0)(NA')A², SA' NA²), SONA'A²; 0-hnked groups including OA¹, OOA¹, OCN, ONA'A²; N- linked groups including NA'A², NAΑ²A^3÷, NC, NA'OA², NA'SA², NCO, NCS, NO,, N=NA\ N=NOA', NA'CN, N=C=NA', NA'NA²A³, NA'NA²NA³A⁴, NA^lN=NA²; other miscellaneous groups including COHal, CON₃, CONA¹,, CONA'COA², C(=NA')NA'A², CHO, CHS, CN, NC, Hal, and deπved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a nng system;

Ak is A¹, A², A³, and A⁴ or X¹, X², X³, X⁴ X⁵...

Hal is F, Cl, Br, or I.

H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlonne, Br is bromine, I is iodine, F is fluonne, R is any cosmetically active, functional group or benefit agent as descnbed herein below.

The invention includes the following preferred non-hmitmg heterocyclic exemplary classes and their X¹, X², X³, X⁴, X⁵... substituted denvatives [Herein referred to as Class I]: - Six membered heterocycles with a single heteroatom such as pyπdme:

- Six membered heterocycles with two heteroatoms such as pynmidmes, pyrazmes and pyπdazmes:

Six membered heterocycles with three and four heteroatoms such as tπazines and tetrazmes:

- Six membered O, N, and/or S containing heterocycles with C=0, C=S or C=C exocyclic groups:

X = O, S, or NX

- Cationic six membered heterocycles with one heteroatom such as pyridinium, pyryhum, and fhiopyryhum salt deπvatives:

- Cationic six membered heterocychcs with two heteroatoms such as pyπmidimum and pyrazmium salt denvatives:

- Five membered heterocycles with one heteroatom such as furans, pyrroles, and thiophenes:

- Five membered heterocycles with two heteroatoms such as pyrazoles, isoxazoles, and isothiazoles:

- Five membered heterocychcs with three heteroatoms such as 1,2,4-tπazoles, 1,2,3-tπazoles, 1,2,4-oxadιazoles, and 1,2,4-thιadιazoles

- Five membered cationic heterocycles with two or more heteroatoms such as pyrazohum and tπazolium:

- Seven membered heterocycles such as azepines, oxepins and thiepms:

Seven membered cationic heterocycles such as thiepimum salts:

and related vaπations including combinations of the above heterocycles m a nng system and fused systems both of which may include carbocyclic nngs without heteroatoms. The cationic heterocycles will also incorporate a Cl^", Br^", I^" or other suitable negatively charged counteπon.

The invention may also include heterocyclic compounds compnsing the cosmetic active, R, that are capable of generating a thiol via a πng-openmg mechanism. Such compounds are represented by the following structures:

wherein at least one cosmetic group, R, comprises or is attached to any of the X¹, X², X³ groups.

Q¹ and Q² represent, independently from one another, a divalent group comparable to A¹ but with the open valencies separated by 0 to 4 atoms.

W¹ represents an electron withdrawing group with a Hammett sigma para value more positive than 0.10 comprising C-linked groups of the classes defined above as A¹, A², A³; S- linked groups including SA¹, SCN, S0₂A\ SO₃A¹, SSA¹, SOA¹, SONA'A², S0₂NAΑ², SNA¹ A², S(NA')A², S(0)(NA¹)A², SA'(NA²); O-linked groups including OA¹, OOA¹, OCN, ONA'A²; N- hnked groups including NA^!A², NA A³*, NC, NA'OA², NA'SA², NCO, NCS, N0₂, N=NA\ N=NOA¹, NA'CN, N=C=NA', NA'NA²A³, NA'NA²NA³A⁴, NA^:N=NA²; other miscellaneous groups including COHal, CON₃, CONA'₂. CONA'COA², C(=NA')NA'A², CHO, CHS, CN, NC,

Hal, and denved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a ring system; L¹ is a suitable leaving group including but not limited to SA¹, OA¹, or NA'A² Below are some non-hmitmg representative examples for each of the above heterocyclic structures (LI through XV) that are capable of generating a thiol via a πng-openmg mechanism

A thiolactone, thiophthahde, and thiazohdinone (classes II, HI and IV),

A dihydrothiophene, dihydrothiopyran, and dιhydro-l,4-thιazιne (classes V, VI and VII),

Unsaturated thiolactones and a dihydrothiapyrone (classes VIII, LX and X),

A dihydrothiepm, thiopyran and thiepmone (classes XI, XII and XIU),

A dihydrothiazolme and 2-methoxythιazolιdme (classes XIV and XV),

and other related denvatives.

Preferred protected thiol compounds of the heterocyclic thiol protective type include the following non-hmitmg examples:

and mixtures thereof, wherein Hal^" is Cl^", Br^", I^" or any suitable negatively charged counteπon.

sp² Aliphatic Trigonal Carbon Protecting Groups - The protecting groups of the present invention may comprise a sp² carbon moiety wherein the divalent sulfur atom is bonded on one side to the cosmetic active and on the other side to a sp" carbon atom. Protecting groups of the sp² aliphatic trigonal carbon type that are suitable for the present invention include (a) aliphatic trigonal carbon atoms double bonded to O, S, N, or C,

M¹

R- -X¹ which includes deπvatives of the following acids: thiocarboxyhc (R-S-C(0)CH₂-A"), carbonodithioic (R-S-C(O)S-A¹, R-S-C(S)O-A'), carbonothioic (R-S-C(O)O-A¹), carbamothioic (R-S-C(0)N-A¹A²), dithiocarboxyhc (R-S-C(S)CH₂-A'), carbonotnthioic (R-S-C(S)S-A¹), carbamoditmoic (R-S-C(S)N-AΑ²), carboximidotmoic

carbommidodithioic (R-S-C(NA')S-A¹), and carbommidothioic (R-S-C(NA')O-A¹) acids Suitable sp² aliphatic tngonal carbon type protecting groups for use in the topical compositions of the present invention do not include carbamimidothioic acids.

The invention also includes (b) related sp² carbon derivatives that are capable of releasing a cosmetic thiol via an intramolecular nucleophihc attack and release mechanism, M¹

M¹

C-

R- C- -Q¹ — Nu R- +

Nu— Q¹ (c) sp² carbon derivatives that are capable of rearranging to produce a cosmetic containing thiol via an intramolecular nucleophihc attack and rearrangement mechanism,

M¹ M¹

R- -E¹ — C- -S Q¹ -Nu R- -E' — C Nu— Q¹ — S^" as well as (d) tngonal carbon electrophiles of the anhydπde, thioanhydπde, and secondary/tertiary amide type,

M¹ M^z

R- -C- -X¹ and related aliphatic tngonal carbon vaπations. The cationic protecting groups will also incorporate a Cl^", Br^", I^" or other suitable negatively charged counteπon.

M¹, M² are O, S, NA¹, NOA¹, NA^]A²⁺, CA^CAV, SA⁺, OA⁺.

E¹ is O, S, NA¹, CAW.

Nu is NHA'A²*, NA'A², OHA¹⁺, OA¹.

X¹ represents an electron withdrawing or electron donating group with a Hammett sigma para value between -1.0 and +1.5 which can be non-ionic, zwittenonic, cationic or anionic compnsing for example C-lmked groups of the classes defined below as A¹, A², A³, S-hnked groups including SA¹, SCN, S0₂A\ S0₃A', SSA¹, SOA¹, SONA'A², S0₂NAΑ², SNA^², S(NA')A², S^^A^A², SA'(NA²); 0-lιnked groups including OA¹, OOA¹, OCN, ONA'A²; N- hnked groups including NA'A², NA¹A²A³⁺, NC, NA'OA², NA^[SA², NCO, NCS, N0₂, N=NA', N=NOA', NA'CN, N=C=NA\ NA^[NA²A³, NA'NA²NA³A⁴, NA'N=NA²; other miscellaneous groups including COHal, CON₃, CONA¹,, CONA'COA², C(=NA¹)NAΑ², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a nng system;

A¹, A² represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly- cychc aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution. Q is a divalent group comparable to A¹ but with the open valencies separated by 2 to 7 atoms.

Y¹ represents electron an withdrawing substituent with a Hammett sigma para value more positive than 0.10. Such electron withdrawing substituents which can be nonionic, zwitteriomc, cationic or anionic include the following non-hmitmg examples: N0₂, CN, COOA¹, CONA'A², C(O)A', S0₂A', S0₂OA', NO, COHal, CON₃, CONA'A², CONA'COA², C(=NA')NA²A³, C(S)A', NC, SCN, S0₂A', S0₃A', SOA¹, S0₂NAΑ², SNA'A², S(NA*)A², S(0)(NA^!)A², NA^[A²A^3τ, SA^]A²⁺.

H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluorine, R is any cosmetically active functional group or benefit agent as descnbed herein below.

Non-hmitmg examples of suitable X¹ groups are as follows:

^N

^•N

₊ .CH₃

/^N

— N

or related derivatives.

Preferred protected thiol compounds of the sp² carbon thiol protective type include the following non-limiting examples:

N(CH₃)₂ ⁺ Br^"

R- ^■OCH₂CH₃

R S- C OCH₂CH₃

O

R- ^■CHj CH, CH, CH, NH₃ ⁺ Cl^*

O

R- -CH, ^•CH, ^■CH, -NH ⁺ Cl^"

O

R- -CH, ^■CH₂ CH₂ CH₂ NH₃ ⁺ Cl^"

sp³ Carbon Protecting Groups The protecting groups of the present invention may comprise an sp³ carbon moiety wherein the divalent sulfur atom is bonded on one side to the cosmetic active and on the other side to a sp³ carbon atom. Protecting groups of the sp³ carbon type that are suitable for the present invention include those of the thioether type,

X¹ ¹ 2 R-S— C-X

^X (I) including the monothioacetal (II. X¹ = H), monothioketal (II. X¹, X² = H), monothioortho ester (LU) and monothioorthocarbonate (IV) type,

X' OA¹ OA^* ¹ 2 I , ¹ 2

R— S— C- X R— S— C-X R— S— C-OA^** ¹ 3

OA¹ (U) O ^A^Λ*- (HI) OA^Υ3 (IV) the dιthιoacetal(V. X¹ = H), dithioketal (V. X¹, X² = H), dithioorthoester (VI) and dithioorthocarbonate (VII) type,

X' OA¹ OA¹ ¹ 2 I j ¹ 2 R— S— C- X² R— S— C- X R-S- C-OA²

SA¹ A^J

(V) SA S

(VI) (VII) the tnthioorthoester type (VLII),

SA¹

I R-S— C-OA^*-

SA^A3 (vm) the thiohemiammal (LX), monothioorthoamide (X) and dithioorthoamide (XI) type, X¹ OA³ SA³

R— S— C ¹ -X 2 R— S— C ' -X 2² R— S— C ' -X I¹

NA'A²^ A'A² _(X) NA'A²^ and related classes wherein X¹, X², X³ represent, independently from one another, electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between -1.0 and +1 5 which can be non-iomc, zwitteriomc, cationic or anionic compnsmg for example C-lmked groups of the classes defined below as A¹, A², A³, S-hnked groups including SA¹, SCN, SO₂A\ SO3A¹, SSA¹, SOA¹, SON^A², S0₂NA'A², SNA'A², S(NA')A², S(0)(NA')A², SA'(NA²); O-lmked groups including OA¹, OOA¹, OCN, ONA^², N-lmked groups including NA'A², NAΑ²A³", NC, NA'OA², NA'SA², NCO, NCS, N0₂, N=NA', N=NOA\ NA'CN, N=C=NA¹, NA'NA²A³, NA'NA²NA³A⁴, NA^:N=NA², other miscellaneous groups including COHal, CON₃, CONA'₂, CONA'COA², C(=NA')NA'A², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a nng system. Hal is F, Cl, Br, or I.

For the thioether class, as defined above, at least one of X¹, X², or X³ groups is electron donating such that the sum of the Hammett sigma para values for X¹, X², X³ is negative for this class.

A¹, A², A³, A⁴ represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly- cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or per fluoro substitution.

H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluonne, R is any cosmetic active, functional group or benefit agent as descnbed herein below.

Preferred electron donating substituents for X¹, X², X³ are aromatic or heteroaromatic denvatives which include the following non-hmitmg examples:

O_.

- .

plus other related derivatives.

Preferred protected thiol compounds chosen from classes I through XI above include the following non-limiting examples:

The present invention also includes organosulfur molecular "hooks" wherein the potential cosmetic thiol is bonded directly to an sp³ carbon atom that is part of a group capable of undergoing heterolytic β-elimination, the reversal of Michael Addition reactions, to liberate a thiol. Suitable sp³ carbon groups capable of undergoing heterolytic β-elimination are represented in the compounds,

H

,γ-

R- CH, — C- -Y¹ R- -S^' + H C^" ^■ C

\

Y^

Y (V) H y

/

R- ^■CH, — C- -Y¹ R- + n H₂,C^* = C

A'

A¹ (VI)

wherein Y¹ and Y² represent, independently from one another, electron withdrawing substituents with a combined Hammett sigma para value more positive than 0 10. Such electron withdrawing substituents include the following non-hmitmg examples: N0₂, CN, COOA¹, CONA'A^", C(0)A', S0₂A\ SO₂OA\ NO, COHal, CON₃, CONA'A², CONA'COA², C(=NA')NA²A³, C(S)A\ NC, SCN, S0₂A', S0₃A\ SOA¹, SONA'A², S0₂NAΑ², SNA'A², S(NA')A², S(0)(NA')A², NA¹ A²A³⁺, SA'A^2" and aromatic and heteroaromatic denvatives.

Some non-hmitmg examples of aromatic and heteroaromatic electron withdrawing groups for Y¹ and Y² include the following:

plus other related denvatives. Prefeπed hook compounds that are capable of undergoing heterolytic β-ehmination, the reversal of Michael Addition reactions, to liberate a thiol include the following non-hmiting examples

O

R- 'CH₂ CH " -CH

O

O

H

R- -CH, -OCH,

OCH,

O

H

R- -CH, -NH,

:0

NH₂

The present invention also includes cases wherein the cosmetic thiol is protected by being bonded directly to an sp³ carbon atom that is incoφorated withm a ring structure. Suitable sp carbon ring systems are represented by the following,

wherein Z is O, NAk, S, (CH₂)₀.₂ or

L¹ is A¹ or part of a 5 to 7 membered fused nng system. The above ring system(s) can carry any substituents. Specific examples of sp³ carbon ring compounds covered by the present invention include the following non-hmiting examples:

and other related derivatives.

A¹, A², A³, represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly- cychc aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can mcoφorate one or more substituents including, but not limited to, poly or per fluoro substitution.

H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluonne, R is any cosmetically active functional group or benefit agent as descnbed herein below.

Metal Based Protecting Groups - The molecular "hooks" of the present invention compnse a divalent sulfur atom that is bonded on one side to the cosmetic active and on the other side to an alkaline earth metal, transition metal or a representative metal in groups ILA, LTJA, IV A, VA, VIA, VILA, Vm, LB, LLB, ΠLB, ΓVB, VB, VLB, and VLLB of the peπodic table of the elements including Mg, Ca, Sr, Ba, La, Ti, Zr, V, Cr, Mo, W, Mn, Fe, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, In, Sn, and Bi. Protected thiol compounds compnsing such heavy metal mercaptides are represented by the following:

R S Met X_n or M_n

R- ^■Met- wherem Met is an alkaline earth metal, transition metal or a representative metal in groups I A, ILIA, LVA, VA, VIA, VILA, Vffl. LB, ILB, LLLB, LVB, VB, VLB, and VILB of the periodic table of the elements including Mg, Ca, Sr, Ba, La, Ti, Zr, V, Cr, Mo, W, Mn, Fe, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, In, Sn, and Bi. Also, wherein n and m are zero or integers such that 1 + 2m + n equals the valency of Met.

X represents independent electron withdrawing, electron neutral or electron donating groups with Hammett sigma para values between -1 0 and +1.5 which can be non-iomc, zwittenomc. cationic or anionic comprising for example C-lmked groups of the classes defined below as A¹, A², A³; S-lmked groups including SA¹, SCN, S0₂A', S0₃A', SSA¹, SOA¹, SONA'A², S0₂NA'A², SNA'A², S(NA')A², S(0)(NA')A², SA'(NA²); O-lmked groups including OA¹, OOA¹, OCN, ONA'A²; N-lmked groups including NA'A², NAΑ²A³⁺, NC, NA'OA², NA'SA², NCO, NCS, N0₂, N=NA', N=NOA^[, NA'CN, N=C=NA', NA'NA²A\ NA'NA²NA³A⁴, NA'N=NA², other miscellaneous groups including COHal, CON₃, CONA'₂, CONA'COA², C(=NA¹)NA'A², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a nng system. Hal is F, Cl, Br, or I.

A¹, A², A³, A⁴ represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly- cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can mcoφorate one or more substituents including, but not limited to, poly or per fluoro substitution.

M is a divalent group such as O, S, NA¹ or CA'A².

H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlorine, Br is bromine, I is iodine, F is fluonne, B is boron, Al is aluminum, Si is silicon, N is nitrogen, Mg is magnesium, Ca is calcium, Sr is strontium, Ba is banum, La is lanthanum, Ti is titanium, Zr is zirconium, V is vanadium, Cr is chromium, Mo is molybdenum, W is tungsten, Mn is manganese, Fe is iron, Co is cobalt, Rh is rhodium, Ni is nickel, Pd is palladium, Pt is platinum, Cu is copper, Ag is silver, Au is gold, Zn is zinc, In is mdium, Sn is tin, Bi is bismuth, and R is any cosmetic active, functional group or benefit agent as descnbed herein below. Also wherein at least one substituent, X, or the cosmetic active, R, contains salt forming or water solubilizmg groups including, but not limited to, COO^", S0₃ , NH₃ ⁺, OH, COOA¹, (CH₂CH₂O)_nA\ CONA'A², OS0₃ ^", OP0₃H\ NA^!A²A^{3^}, and the like.

Preferred metal based proiectmg groups of the present invention include, but are not limited to, the following examples,

N(CH₃)₂ R-S— Ti-N(CH₃)₂ N(CH₃)₂

O

I I

R— S- V-S— R

I

S-R

CH₂CH₃ R-S— Sn-CH₂CH₃ CH₂CH₃

OCH2CH2CH2CH3

R-S— Ti-OCH2CH₂CH₂CH3 OCH2CH2CH2CH3

R— S-Ni-S— R

S-R I R-S-Mo-S— R

I

^{S— R} , and

OCH2CH2CH2CH₃ R— S— &-OCH2CH2CH2CH3 OCH2CH2CH2CH3 Non-metal and metalloid based Protecting Groups - The molecular "hooks" of the present invention compnse a divalent sulfur atom that is bonded on one side to the cosmetic active and on the other side to a representative non-metal or metalloid atom including boron, aluminum, silicon, germanium, nitrogen, phosphorus, sulfur, selenium, antimony, and tellurium. Molecular "hooks" whereby a divalent sulfur atom of a potential cosmetic thiol is bonded directly to these representative non-metals and metalloids are represented by the following

R S E X_n or _m

R S E X_n wherein E is a representative non-metal or metalloid element including B, Al, Si, Ge, N, P, S, Se, Sb, and Te. Also, wherein n and m are zero or integers such that 1 + 2m + n equals the valency of E.

X represents independent electron withdrawing, electron neutral or electron donating groups with Hammett sigma para values between -1.0 and +1.5 which can be non-iomc, zwittenomc, cationic or anionic compnsmg for example C-lmked groups of the classes defined below as A¹, A², A³; S-lmked groups including SA¹, SCN, S0₂A', S0₃A', SSA¹, SOA¹, SONA'A², S0₂NA'A², SNA' A², S^A^A², S(0)(NA')A², SA'(NA²); O-linked groups including OA¹, OOA', OCN, ONA'A²; N-lmked groups including NA'A², NA^A^3*, NC, NA'OA², NA'SA², NCO, NCS, N0₂, N=NA', N=NOA\ NA'CN, NONA¹, NA'NA²A³, NA'NA²NA³A⁴, NA'N=NA²; other miscellaneous groups including COHal, CON₃, CONA'₂, CONA'COA², C(=NA')NA'A², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a nng system. Hal is F, Cl, Br, or I.

M is a divalent group such as O, S, NA¹ or CA'A².

H is hydrogen, O is oxygen, N is nitrogen, C is carbon, S is sulfur, Cl is chlonne, Br is bromine, I is iodine, F is fluonne, B is boron, Al is aluminum, Si is silicon, Ge is germanium, N is nitrogen, P is phosphorus, Te is telluπum, and R is any cosmetic active, functional group or benefit agent as described herein below.

Preferred thiol protective systems utilizing non-metals and metalloids of the present invention include, but are not limited to, the following examples,

OCH₂CH₃ R-S— Si-OCH₂CH₃ OCH₂CH₃

CH₃

I R— S— Si-CH.₃ I CH₃

O

II R— S— S— CH₃ II O

R— S— B— S— R I S- R

O O

II

R-S-Ge-O-Ge-S— R , and

S-R I R-S— Sb-S- R I S-R

Energy-sensitive Protecting Groups - The topical compositions of the present invention may also compnse a protected thiol compound wherein the protecting group is energy-sensitive. Protected thiol compounds comprising energy-sensitive protecting groups are chemically stable in solution. Such potential thiols are protected until a suitable source of energy is applied to the composition. Upon application of a suitable energy source, the energy-sensitive protecting groups become labile, thereby releasing the reactive thiol Typically, the energy source will be light. Once the thiols are released, they are capable of reacting with amino acid residues present in keratmaceous substrates to enable durable cosmetic benefits.

As mentioned above, the protected thiols are activated by applying a suitable energy source to the composition, i.e., irradiation, which converts the photoactivatable protected thiol compounds to fully reactive thiol compounds. The byproducts of the energy activation of the protecting group will usually be removed from the substrate by washing.

Many different energy-sensitive groups can be employed for protecting thiols used in the topical compositions of the present invention. Typically, the thiol groups are protected with a photoactivatable protecting group that is capable of liberating or releasing the reactive thiol by irradiation The properties and uses of photoreactive compounds have been reviewed. See McCray et al, 1989, Ann. Rev Biophys Chem 18:239-270, which is incoφorated herein by reference. The photosensitive groups will preferably be activatable by low energy ultraviolet or visible light. Many, although not all, of the energy-sensitive protecting groups are aromatic compounds. Suitable photoremovable protecting groups are also descnbed in, for example, Patchomik, 1970, J Am. Chem. Soc 92:6333, and Amit et al, 1974, / Org Chem 39: 192, which are mcoφorated herein by reference. More preferably, the energy-sensitive protecting group will be a nitrobenzyhc compound, such as o-nitrobenzyl or benzylsulfonyl groups. Suitable examples include 6-nitroveratryloxycarbonyl (NVOC); 6-mtropιperonyloxycarbonyl (NPOC); alpha, alpha-dimethyldimethoxybenzyloxycarbonyl (DDZ), methyl 6-nιtroveratryloxycarbonyl (MenVOC), methyl-6-mtropιperonyloxycarbonyl (MeNPOC), or 1-pyrenylmethyl. The energy- sensitive protecting group may also be of the silyl type as descnbed m Pirrung and Lee, 1993, J Org Chem. 58:6961-6963 and Pirrung and U.S. Patent Number 5,486,633, issued to Lee, both incoφorated by reference herein. Suitable examples include (hydroxystyryl)dιmethylsιlyl (HSDMS) and (hydroxystyryl)dusopropylsιlyl (HSDIS).

Clearly, many energy-sensitive protecting groups are suitable for use in the present method. Some examples of acceptable energy-sensitive protecting groups are presented in Table 1, below, together with their corresponding wavelengths for deprotection.

TABLE 1 Energy-sensitive Protecting Groups

Deprotection Group Wavelength

6-nιtroveratryloxycarbonyl (NVOC) UV (300-350 nm) dimethyldimethoxybenzyloxycarbonyl (DDZ) UV (280-300 nm) mtrobenzyloxycarbonyl (NBOC) UV (300-350 nm) 5-bromo-7-nιtromdohnyl (BNI) UV (420 nm) O-hydroxy-alpha-methyl-cinnamoyl (HMC) UV (300-350 nm) 2-oxymethylene anthraquinone (OMA) UV (350 nm)

The composition containing the cosmetic active protected with the energy-sensitive group may be activated with energy both pπor or during usage. For instance, the energy source may be applied to the composition for a sufficient time penod to activate the energy sensitive protecting group either before, duπng or after the composition is applied to the substrate. The energy source may include vanous types of electromagnetic radiation including ultraviolet, visible, near infrared, infrared, far infrared or microwave. In a preferred embodiment, the radiation is UV, near LR or visible light.

Examples of suitable protecting groups that are capable of undergoing photochemical or thermal thiol deprotection include, but are not limited to, the following:

I 2-Nιtrobenzyl derivatives

Examples:

LL 2-Nιtrobenzyloxycarbonyl Denvatives

Examples:

LLI. Benzyloxycarbonyl Derivatives -SH + Side products

Examples:

IV. α.α-Dimethylbenzyloxycarbonyl Derivatives

Example:

V. 3 -Nitrophenyloxycarbonyl Derivatives

Example:

VI Phenacyl Derivatives

Examples:

VIL tert-Butyloxycarbonyl Denvatives

CH₃ O

I II heat CH₃— C-O-C-S- R ► R-SH + CO₂ + CH₃-C=CH₂

I ^l I

CH₃ CH₃

X¹, X², X³, X⁴ _, and X⁵ can be selected from electron withdrawing, electron neutral, or electron donatmg groups with Hammett sigma para values between -1.0 and +1.5 which can be non-ionic, zwitteπomc, cationic or anionic compnsing for example C-lmked groups of the classes defined below as A¹, A², A³; S-lmked groups including SA¹, SCN, S0₂A', SO₃A\ SSA¹, SOA¹, SONAV, SO_JNA'A², SNA¹ A², S(NA')A², S(0)(NA')A², SA'(NA²); O-lmked groups including OA¹, OOA¹, OCN, ONA'A²; N-hnked groups including NA'A², NAΑ²A³⁺, NC, NA'OA², NA'SA², NCO, NCS, N0₂, N=NA', N=NOA', NA'CN, NONA¹, NA'NA²A³, NA'NA²NA³A⁴, NA'N=NA²; other miscellaneous groups including COHal, CON₃, CONA'₂, CONA'COA², C(=NA')NA'A², CHO, CHS, CN, NC, Hal, and deπved groups that connect one or more of X¹, X², X³, X⁴, X⁵ via a nng system;

A¹, A² represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or poly- cyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incoφorate one or more substituents including, but not limited to, poly or per fluoro substitution Mono or Multivalent Cosmetically Active Functional Group

The mono or multivalent cosmetically active functional, R, suitable for inclusion in the present invention may be any compound that imparts one or more visual, tactile or other cosmetic beneficial effects on proteinaceous matenals such as keratin, i.e., hair, animal fur or wool. Any cosmetic compound may be included as a functional group in the compositions of the present invention as long as the compound can be modified to contain at least one divalent sulfur atom linked to a suitable protecting group as descnbed herein.

Suitable functional groups that can be protected as thiol denvatives include but are not limited to antimicrobial compounds, UV-absorbmg compounds, skin conditioning agents, hair conditioning agents, hair repair agents, hair styling agents, hair dyes, scalp treatment agents, anti- inflammatory compounds, antioxidants, dyes and colonng agents, perfumes, oral care actives, skm moistunzers, pharmaceutical agents, antidandruff agents, insect repellents, moistunzers, humectants, pearlescent and/or opacifying mateπals, fabπc care actives, pet grooming actives, fabric anti-wπnklmg agents, shπnk-resistant actives, laundry care actives, hard surfaces actives, textile actives, textile dyes, water-proofing agents, cationic polymers, cationic surface modifiers, hydrophobic surface modifiers, anionic surface modifiers, absorbents, antifungal agents, msecticidal agents, textile color guards, nail actives such as enamel and polish, eyelash actives and mascara, antiperspirant and deodorant actives, anti-acne actives, odor control actives, fluorescent actives, bleaching agents, enzymes, antibodies, dispersing aids, emollients, stabilizers, anti-static agents, anti-seborrhea agents, optical bπghteners, fluorescent dyes, softeners, cross-linking agents, photobleaches, bactencides, and mixtures thereof.

Examples of suitable antimicrobials which can be protected as thiol denvatives include but are not limited to denvatives of phenol, cresol, hydroxybenzoates, Tnclosan®, Tπcarban®, chlorhexidme, metal salts (e.g. zmc citrate, sodium zmc citrate, zinc pyndmethione, and stannous pyrophosphate) sangumaπne extract, metromdazole, quaternary ammonium compounds (chlorhexidme digluconate, hexetidione, octenidme, alexidme), halogenated bisphenohc compounds such as 2,2'-methylenebιs-(4-chloro-6-bromophenol), and salicylanihde.

Examples of suitable UV-absorbmg matenals which can be protected as thiol derivatives include but are not limited to denvatives of benzoates, oxybenzones, cmnamic acid, PARSOL MCX esters, benzotnazoles, and benzophenones. Examples of suitable skm conditioners or moisturizers which can be protected as thiol denvatives. include but are not limited to derivatives of alpha-hydroxy acids, polyols, hyaluronic acid, petrolatum, vegetable oils, esters of fatty acids, and mineral oil Such skin conditioners or moisturizers are bound to the velus hairs present on the skin, and not the skm directly, to achieve the long lasting skin benefits.

Examples of suitable anti-inflammatory agents which can be protected as thiol derivatives include but are not limited to corticosteroids or sahcylates.

Examples of suitable antioxidants which can be protected as thiol derivatives include but are not limited to ascorbates and gallates.

Examples of suitable hair conditioners which can be protected as thiol denvatives include but are not limited to mtact or modified proteins, such as hydrolyzed keratm, collagen, elastin, hemoglobin, silk, rice, soy, wheat protein, corn, fibronectin, reticulum, serum protein, wheat gluten, peptides and peptide denvatives; amino acids; hydroxylated fats; glycinates; silicone polymers, such as siloxane gums and resins, volatile or non-volatile silicone oils, ammo- (or other) functional silicones, and other sihcone-contammg polymers; hydrocarbon based conditioners including C₈-C₃₀ alkyl, alkenyl, modified alkyl or modified alkenyl, branched alkyl and branched alkenyl groups as well as long chain alkyl groups that are ethoxylated or substituted with vanous non-ionic, cationic or anionic functional groups including quats, ammes, amides, esters, hydroxyls, carboxylates, and the like, polysacchaπdes or monosacchandes, and alkyl cationic conditioning polymers such as cationic denvatives of guar gum and cellulose ether denvatives; poly(ethyleneoxιdes) and alkyl capped poly(ethyleneoxιdes) of molecular weights ranging from 100 to 10,000,000; and herb or other plant extracts, essential oils etc.

Examples of suitable hair styling agents which can be protected as thiol denvatives include but are not limited to film-forming polymers such as polyvinylpyrrohdone/vmyl acetate copolymer; styling copolymers compnsing silicone macromonomers, U.S. Patent Nos. 5,618,524 and 5,658,557, cationic polymers, such as those disclosed in GB-A-2161172 (Beecham), GB-A- 2122214 (Unilever) and GB-A-2050166 (L'Oreal); and hydrocarbon polymers, such as polyisobutylene; perfluoro-aliphatic and perfiuoro-aromatic compounds.

Examples of suitable dyes and colonng agents which can be protected as thiol denvatives include but are not limited to phenol, naphthols, acid dyes, azo denvatives; vegetable dyes, metallized dyes, nitrobenzene dyes, qumone-imme dyes, basic dyes, quaternary dyes, and oxidation dyes.

Examples of suitable fragrances that can be protected as thiol denvatives include but are not limited to phenols such as menthyl salicylate, thymol, and vanillin. Examples of suitable cationic polymers that can be protected as thiol derivatives include but are not limited to denvatives of quaternary ammonium salts of hydroxyethylcellulose, cationic copolymers of acrylic acid and acrylamide, cationic guar polymers, copolymers of vinylimidazohum methochloπde and vinylpyrrohdone, polyethylemmines, and other cationic polymers and resms known to those skilled m the art.

Examples of suitable oral care active agents that can be protected as thiol denvatives include but are not limited to anti-canes agents such as amine fluorides, monosodium fluorophosphate, casem; plaque buffers such as urea, calcium lactate, calcium glycerophosphate; anti-plaque agents, agents for alleviating sensitive teeth, e.g. potassium and strontium salts, particularly those of carboxylic acids; matenals that form films and block pores, oral pharmaceutical actives, (e.g. ibuprofen, flurbiprofen, aspiπn and indomethacin), biomolecules such as peptides, antibodies and enzymes; anti-tartar agents; agents for treating bad breath such as zmc salts; and anti-calculus agents (e.g. alkali metal pyrophosphates, hypophosphite- contaming polymers, organic phosphonates, and phosphocitrates).

Examples of suitable pharmaceutical agents that can be protected as thiol denvatives include but are not limited to medicinal agents, metabolic agents and other therapeutic agents of benefit in treating the human body.

Examples of antidandruff agents that can be protected as thiol denvatives include but are not limited to zinc pyndmethione, Octopirox®, chmbazole and ltroconazole.

An example of odor control actives that can be protected as thiol denvatives include the class of cyclodextnns. In addition to trapping odors on the substrate, the cyclodextnns can plausibly be utilized to deliver cosmetic actives molecules to the substrate such as perfumes that can be liberated slowly.

Other non-hmiting classes of beneficial cosmetic actives include sealants, binders, resms, adhesives, waxes, drying oils, varnishes, and latex finishes which compπse urethanes, polysulfides, acrylics, butyl polymers, maleated oils, cellulosics, starches etc.

The mono or multivalent cosmetically active functional preferably used in the present compositions is dependent on the product form desired. Hair care compositions preferably use hair conditioners, hair styling agents, dyes and colonng agents, sunscreens, fragrances, antidandruff agents, or mixtures thereof as the functional group. Preferable functional groups in textile care compositions include dyes and colonng agents, odor control actives, sealants, fragrances, and mixtures thereof. Cosmetic compositions preferably compnse dyes and colonng agents, sealants, resms, varnishes, latex finishes, and mixtures thereof. Oral care compositions preferably compπse anti-canes agents, plaque buffers, anti-plaque agents, agents for alleviating sensitive teeth, mateπals that form films and block pores, oral pharmaceutical actives, biomolecules, anti-tartar agents, agents for treating bad breath, anti-calculus agents, and mixtures thereof as functional groups. Pharmaceutical composition preferably select mono or multivalent cosmetically active functional groups from the group consisting of medicinal agents, metabolic agents, therapeutic agents, anti-inflammatory compounds, and mixtures thereof Animal care composition preferably compnse antimicrobial agents, insect repellents, grooming actives, and mixtures thereof as functional groups. OPTIONAL ACTIVATING MECHANISMS

As explained above, the molecular 'hooks' of the present invention may be activated via a number of mechanisms either before, dunng or after the application of the topical compositions containing the protected thiol to the substrate. Vanous embodiments of the present invention are systems which compπse both the topical composition herein with an activating mechanism.

Such activation could be achieved via hydrolysis by the use of a mechanism to manipulate the pH of the environment surrounding the compound. Such pH adjusting mechanisms may include acidic or alkaline solutions. Whether acidic or alkaline mechanisms are required is dependent on the protecting group used. Hydrolysis may also be achieved via simply mixing the compound, delivered m its puπfied form or from a non-aqueous solution, with water.

Furthermore, the molecular 'hook' could be activated by coming m contact with a suitable nucleophile Such nucleophiles include, but are not limited to, nitrogen-containing functional groups, for example amines, oxygen-containing functional groups, for example hydroxyl groups, phosphorus-containing functional groups, for example phosphmes, and sulfur-contammg functional groups, for example thiol groups and sulfites. For instance, the solution containing the 'hook' compound could be inter-mixed with a separate solution containing a nucleophile including reducmg agents such as ammonium thioglycolate or sodium bisulfite, either before, duπng or after application of the compound to the substrate.

Conversely, the 'hook' compound could be activated by nucleophihc groups present in the substrate itself as in the case of hair that has been reduced or cold waved, i.e. hair that has been treated with a reducing agent either pnor to or simultaneous to the application of the 'hook' compound. The resultmg activated thiol 'hook' could then react directly as a nucleophile with keratmaceous disulfϊdes or oxidatively with the nucleophihc groups present in the substrate, e.g. with free thiol groups that were formed duπng cold waving or reduction. Of course, the latter process could be accelerated or enhanced via the addition of oxidation reagents, i.e. peroxide as in the neutralization step of cold waving of hair. The activation could also be accented via heat or a suitable energy source. For instance, the energy source could be applied to the composition for a sufficient time period to activate the protecting group either before, during or after the composition is applied to the substrate. The energy source may include various types of electromagnetic radiation including ultraviolet, visible, near infrared, infrared, far infrared or microwave radiation.

Other vanous adjuncts that could possibly influence the activation and/or the performance of the "hook" compounds of the present invention include, but are not limited to, (1) Lewis acids such as zmc acetate, tin chlonde, zinc chlonde, zmc stearate, titanium ethoxide, and aluminum tosylate, metal salts such as zmc sulfate, and magnesium sulfate, (n) chelators such as tetrasodium EDTA, disodium EDTA, (in) ionic species capable of lon-painng including anions, cations, quats, amphoteπcs zwittenons etc, (IV) dispersing aids such as anionic surfactants, nonionic surfactants, anionic surfactants, amphoteric surfactants, and zwittenonic surfactants, (v) keratm swelling aids such as ammonia, amines, urea, phosphonc acid, acetic acid and other swelling aids known to those skilled in the art, and (vi) solvent systems wherein the individual solvent molecules are nucleophiles themselves as defined above.

Another embodiment of the present invention compnses a kit compnsing the system compns g the topical compositions of the present invention and either a pH manipulating mechanism or a nucleophile mechanism, and a package compnsmg a first and second chamber; wherein the topical composition is packaged in and delivered out of one chamber and the activation mechanism is packaged in and delivered out of the second chamber. OTHER OPTIONAL INGREDIENTS

The topical composition according to the invention can also typically include an acceptable vehicle to act as a dilutant, dispersant, or earner for the protected thiol compounds in the composition, so as to facilitate the distribution of the protected thiol compounds when the composition is applied to the keratmaceous substrate, i.e., hair, nails, wool, sk etc.

Vehicles other than water can include liquid or solid emollients, solvents, humectants, thickeners and powders. Examples of each of these types of vehicle, which can be used singly or as a mixture of one or more vehicles, are as follows:

Emollients, such as stearyl alcohol, glyceryl mononcmoleate, glyceryl monostearate, mink oil, cetyl alcohol, isopropyl isostearate, steanc acid, isobutyl palmitate, lsocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isododecane, lsocetyl alcohol, eicosanyl alcohol, behenyl alcohol, cetyl palmitate, silicone oils such as polydimethylsiloxane, cyclomethicone, di-n-butyl sebacate, isopropyl myπstate, isopropyl palmitate, isopropyl stearate, butyl stearate, dimethyl malonate, polyethylene glycol, tπethylene glycol, lanolm, cocoa butter, com oil, cotton seed oil, tallow lard, olive oil, palm kernel oil, rapeseed oil, safflower seed oil, evening primrose oil, soybean oil, sunflower seed oil, avocado oil, olive oil, sesame seed oil, coconut oil, arachis oil, castor oil, acetylated lanolin alcohols, petroleum jelly, mineral oil, butyl myπstate, isosteaπc acid, palmitic acid, isopropyl linoleate, lauryl lactate, mynstyl lactate, decyl oleate, mynstyl mynstate;

Propellants, such as tnchlorofluoromethane, dichlorodifluoromethane, dichlorotetrafluoroethane, monochlorodifluoromethane, tnchlorotπfluoroethane, propane, butane, isobutane, dimethyl ether, carbon dioxide, nitrous oxide;

Solvents include, but are not limited to, ethyl alcohol, n-propanol, n-butanol, tert-butanol, ethylene glycol dimethyl ether, hexane, tetramethylurea, sulfolane, low molecular weight poly(ethylene oxide), glycerol, propylene glycol, 2-butoxyethanol, amyl alcohol, n-octanol, n- decanol, acetone, acetic acid, butyl acetate, methylene chlonde, isopropanol, acetone, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulphoxide, dimethylformamide, tetrahydrofuran;

Powders, such as chalk, talc, fullers earth, kaolm, starch, gums, colloidal silica, sodium polyacrylate, tefraalkyl- and/or tnalkyl-arylammomum smectites, chemically modified magnesium aluminum silicate, organically modified montmoπllonite clay, aluminum silicate, fumed silica, carboxyvmyl polymer, sodium carboxymethylcellulose, ethylene glycol monostearate.

The cosmetically acceptable vehicle will usually form from 10 to 99.9%, preferably from 50 to 99% by weight of the composition and can, in the absence of other cosmetic adjuncts, form the balance of the composition.

The topical compositions according to the invention may be provided in any suitable physical form, for example as low to moderate viscosity liquids, lotions, milks, mousses, dispersions, sprays, gels, foams, aerosols, and creams. These compositions may be produced by procedures well known to the skilled artisan. The cosmetic compositions can be used m vanous manners as other known compositions in the art including but not limited to vanous nnse-off and leave-on applications such as hair shampoos, skm cleansers, skm lotions, hair conditioners, styling sprays, hair mousses, two-m-one shampoos, fabnc softeners, lotions, nail polishes, hair serums, hair dyes, hair waving, etc. The contact time between the cosmetic composition of the present invention and the substrate vanes between 10 seconds and about 1 hour, preferably between 20 seconds and 30 minutes, more preferably between 30 seconds and 15 minutes.

The cosmetic composition of the present invention can be formulated as a fluid, lotion, fluid cream or cream having a viscosity from 500 to 100,000 mPas or above. The composition can be packaged in a suitable container to suit its viscosity and intended use by the consumer For example, a lotion or fluid cream can be packaged in a bottle or a roll-ball applicator or a propellant-dnven aerosol device or a container fitted with a pump suitable for hand or finger operation. When the composition is a cream, it can simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar

The topical product or composition of the present invention may include an activator as descnbed above In such a case, the inventive composition must be designed to prevent premature activation of the protected thiol compound pnor to use. For instance, the protected thiol compound and the activator may be placed in separate chambers in a dual chamber package, or either of the 'hook' compound or the activator can be placed with shear sensitive (or other induced release) capsules which rupture pπor or duπng use. Alternatively, the protected thiol compound and the activator can be placed in separate packages to enable pre-mixmg or sequential application by the consumer. For examples of typical dual chamber packages see PCT Application WO 96/02230, by Unilever PLC, published February 1, 1996. (Herein mcoφorated by reference.)

Conversely, the cosmetic active of the present invention can be supplied in the punfied form, i.e., as a powder, crystal, wax, gum or liquid. The punfied cosmetic active could be intermixed with any of the above suitable earners either pnor to or simultaneous to the usage by the consumer. For instance, the punfied cosmetic active could be placed withm a compartment that is separated from the earner by a bamer wall. Upon usage, the barrier wall could be broken, disrupted or even removed to enable the punfied cosmetic active to come m contact with and mter-mix with the earner.

The topical composition of the present invention compnses at least one of the above descnbed protected thiol compounds, together with any additional ingredients which are normally to be found m cosmetic treatment compositions for use on hair, skm, or other substrates such as other fibers, textiles, fabπcs, or the like. One or more of the protected thiol compounds may be used, the use of two or more being beneficial for example where a combination of cosmetic benefits is wanted, each denvable from a different cosmetic agent species.

While aqueous or aqueous/alcoholic solution based compositions, or possibly organic- based compositions, m which one or more protected thiol compounds are dissolved by solution are preferred, the compositions if desired or appropπate may compnse stable emulsions or dispersions of the one or more functionahzed cosmetic agents which are designed to be water insoluble. In both of these cases, conventional means for achieving successful deposition and activation of the actιve(s) may be required, for instance, an emulsion or a dispersion could be intermixed with a separate solvent solution via a dual phase package to enable solubihzation and subsequent activation duπng usage

The topical composition according to the invention may include optional benefit materials and cosmetic adjuncts, as long as the benefit matenals or the adjuncts do not eliminate or substantially reduce the performance of the organosulfur functionahzed cosmetic agent. The additional ingredients may include, for example dyes and colonng agents, fragrances; anionic, cationic, non-ionic, amphotenc or zwitteπonic surfactants; buffers, masking fragrances, dispersing agents, stabilizers, cationic polymers, perfumes, non-ionic polymers, anionic polymers, complex coacervates, complex coacervate capsules, metal salts, Lewis acids, buffering agents, particulate thickeners, polymeπc thickeners, wax thickeners, oils, emollients, humectants, moistunzers, dyes, dyes and colonng agents, enzymes, antibodies, preservatives, viscosity enhancers, gelling agents, chelators, silicones or other emulsifying agents, and other common adjuvants well known to those skilled in the art.

Nonlimiting examples of anionic lathenng surfactants useful m the compositions of the present invention are disclosed m McCutcheon's, Detergents and Emulsifiers, North Amencan edition (1990), published by The Manufactunng Confectioner Publishing Co.; McCutcheon's, Functional Matenals, North Amencan Edition (1992); and U.S. Patent No. 3,929,678, to Laughlm et al., issued December 30, 1975, all of which are incoφorated by reference.

A wide vanety of anionic surfactants are potentially useful herein. Nonlimiting examples of anionic lathenng surfactants include those selected from the group consisting of alkyl and alkyl ether sulfates, sulfated monoglycendes, sulfonated olefins, alkylaryl sulfonates, pπmary or secondary alkanesulfonates, alkyl sulfosuccinates, acyltaurates, acyhsethionates, alkyl glyceryl ether sulfonates, sulfonated methyl esters, sulfonated fatty acids, alkyl phosphates, acylglutamates, acylsarcosinates, alkyl sulfoacetates, acylated peptides, alkyl ether carboxylates, acyllactylates, anionic fluorosurfactants, and mixtures thereof. Mixtures of anionic surfactants can be used effectively in the present invention.

Suitable nonionic surfactants include polyoxyalkylene alcohol surfactants, especially alkyl polyethyleneglycol ethers, alkyl polypropyleneglycol ethers, alkyl polyethyleneglycol esters, and alkyl polypropyleneglycol esters and mixtures thereof.

Suitable amphotenc surfactant components for use in the shampoo composition herein include those which are known for use in shampoo compositions or other personal care cleansing composition, and which contain a group that is anionic at the pH of the shampoo composition Concentration of such surfactant components m the shampoo composition preferably ranges from about 0.5 % to about 20%, preferably from about 1% to about 10%, more preferably from about 2% to about 5% by weight of the composition Examples of amphotenc surfactants suitable for use in the shampoo composition herein are descnbed in U S Patents 5,104,646 (Bohch Jr et al ), U S Patent 5,106,609 (Bohch Jr et al ), which descπptions are incoφorated herein by reference Examples of amphoteric detersive surfactants which can be used in the compositions of the present invention are those which are broadly descnbed as denvatives of aliphatic secondary and tertiary amines m which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic water solubilizmg group, e g., carboxy, sulfonate, sulfate, phosphate, or phosphonate Examples of compounds falling withm this definition are sodium 3-dodecylamιnopropιonate, sodium 3-dodecylammopropanesulfonate, sodium laurylsarcosmate, N-alkyltauπnes such as the one prepared by reacting dodecylamme with sodium lsethionate according to the teaching of U S Patent 2,658,072, N-higher alkyl aspartic acids such as those produced according to the teaching of U S Patent 2,438,091, and the products sold under the trade name "MLRANOL"™ and described in U S. Patent 2,528,378

Other amphotenc surfactants, sometimes classified as zwittenonic surfactants, such as betames can also be useful in the present invention Such zwitteπonics are considered as amphotencs in the present invention where the zwitteπonic has an attached group that is anionic at the pH of the composition Examples of betaines useful herein include the high alkylbetames, such as cocodimethylcarboxymethylbetaine, cocoamidopropylbetaine, cocobetame, laurylamidopropylbetame, oleylbetaine, lauryldimethylcarboxymethylbetame, lauryldimethyl- alpha-carboxyethylbetaine, cetyldimethylcarboxymethylbetaine, lauryl-bιs-(2- hydroxyethyl)carboxymethylbetame, stearyl-bιs-(2-hydroxypropyl)carboxymethyl betame, oleyldimethyl-gamma-carboxypropylbetame, and lauryl-bιs-(2-hydroxypropyl)-alpha- carboxyethylbetame. The sulfobetaines may be represented by cocodimethyl sulfopropylbetame, stearyldimethylsulfopropylbetaine, lauryldimethylsulfoethylbetame, lauryl-bιs-(2- hydroxyethyl)sulfopropylbetame and the like; amidobetaines and amidosulfobetames, wherein the RCON(CH ) radical is attached to the nitrogen atom of the betame are also useful m this invention Most preferred for use herein is cocoamidopropylbetaine.

If desired or as necessary, one or more additional benefit agents may also be included in the compositions of the invention, for example to modify the overall cosmetic benefit or combination of benefits imparted to the substrate treated with the composition Suitable additional cosmetic benefit agents include the following. (1) conditioning agents, i.e., mateπals which impart one or more visual or tactile benefits such as softness, smoothness, shme, non-flyaway, anti-static, ease of dry and/or wet combing, e g , cationic surfactants, cationic polymers, volatile and/or non-volatile silicones or derivatives thereof, quaternary ammonium salts having at least one long chain alkyl or alkenyl group, protein hydrolysates, quaternized protein hydrolysates, perfluoropolyether mateπals, fatty alcohols, and mixtures thereof;

(n) stylmg/settmg bodying agents, i.e., matenals which give enhanced body and fell to the hair or other fibers or enable them to hold a given shape or style, e.g., various polymers, gums and resins, for example adhesive and/or resinous hydrocarbon mateπals such as per- alk(en)ylhydrocarbon materials, sihcone/siloxane gums or resins, waxes, chitosan and denvatives, salts and complexes thereof, and mixtures thereof;

(in) fiber straightening agents;

(iv) colourants and dyeing agents;

(v) antidandruff agents, e.g., zmc pyndmethione, Octopirox®, chmbazole;

(vi) sun-protective matenals, e.g. sunscreens, especially UV absorbers;

(vπ) hair growth promoters or regulators, e.g. diacylglycerols, glucarolactams, glucarolactones, Mmoxidol®;

(vm) moistunzers, e.g. 2-hydroxyalkanoιc acids, acid soap and complexes thereof, and other emollients, occlusives, humectants;

(IX) pearlescent and/or opacifying mateπals;

(x) oils, e.g. silicone oils, oleic acid, hydrocarbons, isopropyl myπstate, oleyl alcohol, oleates, squalene, sunflower seed oil, rapeseed oil, other plant deπved oils, mineral oil;

(xi) proteins, vitamins, nutπents, stimulants, antiradicals, astnngents;

(xn) herb or other plant extracts, essential oils etc.

(xin) antimicrobial agents, e.g. antibacteπal or anti-mfestive agents;

(xiv) other adjunct mateπals commonly used m cosmetic compositions, e.g., buffenng and/or pH adjusting agents, perfumes, colorings, preservatives, proteins etc.

(xv) anti-malodor agents as those disclosed to treat post-perm odors in US 5,554,364 and EP 0610892.

(xvi) highly substantive polymers and other moieties including polyethylenimines (PEI's) such as those included withm the Polymm® senes supplied by BASF.

(xvn) metal salts compnsmg alkaline earth metals such as magnesium and calcium, transition metals such as zmc, manganese and copper, and the group LTIA metals such as Al. The use of these metal salts for hair treatment is disclosed m WO9609030 and WO9703640 where they are claimed to form metal-sulfur bonds with the hair for use m hair styling and restyhng. Such metal salts could conceivably be employed to complex and interact with the cosmetic active of the present invention. Such interactions should not interfere too greatly with the performance of the cosmetic actives and could potentially positively influence the performance, i.e., metals could complex with the sulfur atom withm cosmetic active and facilitate or induce activation m the form of thiol release

(xvui) chelating agents including disodium EDTA and tetrasodium EDTA. Chelators could enhance the diffusion and adsoφtion by binding to and removing metals present in hard water such as calcium and magnesium. Such hard water ions could conceivably complex with certain ionized "hooks" of the present invention electrostatically and inhibit their solubility.

(xix) hydrotropes such as ammonium xylene sulfate. For instance, if the "hooks" of the present invention are incoφorated with a surfactant matrix, hydrotropes could improve performance by freeing up the "hook" compounds duπng dilution to facilitate improved binding to the substrate.

(xx) dispersing aids which may encompass, but are not limited to, non-iomc surfactants, amphotenc surfactants, and ionic surfactants. If the "hooks" of the present invention are incoφorated withm a non-aqueous matπx of as an insoluble dispersion, dispersing aids could be utilized to enhance solubihzation and subsequent activation.

(xxi) Ion-pair ingredients. For certain ionic "hooks" of the present invention, compounds could be employed that ion-pair with the "hooks" including, but not limited to cations, anions, quaternized ammonium compounds, amphotenc compounds, and metals. Such charged species could be utilized to manipulate the diffusion, adsoφtion and the binding of the "hook" compounds of the present invention.

(xxn) Drying agents designed to minimize residual levels of water m non-aqueous solvent, including, but not limited to molecular sieves.

The pH of the compositions of the present invention is frequently important in achieving optimized chemisoφtion of the protected thiol compound. The most suitable pH for a given composition may depend pnncipally on the type and structure of the protecting group as it pertains to activation. For instance, many of the protecting group can be activated for improved performance via pH catalyzed hydrolysis. In these cases, the pH of the composition would need to be such that the molecular 'hook' is not activated pnor to usage. As descnbed above, duπng usage the pH of the composition containing the molecular 'hook' can be manipulated, i.e., via mter-mixmg with separate pH activating composition, such that the molecular 'hook' is activated duπng or immediately pπor to usage.

The protecting groups of the present invention are to be used withm a pH range from about 1 to about 12, preferably from about 3 to about 11, more preferably from about 4 to about 10. In the cases wherein the protecting group are activated at any of the above pH's, the composition would need to be non-aqueous and essentially free of water or moisture to such a degree that prohibits significant hydrolysis induced activation prior to usage. As such, the water imparted to the composition during usage from the shower, bath or from the wetted substrate could provide the activation required to optimize the resulting chemisoφtion.

As mentioned above, it has suφπsmgly been found that certain protecting groups are not activated hydrolytically at pH's withm the above ascnbed relevant range while still providing durable benefits on hair. For these compounds, the pH of the composition is irrelevant in as much as the composition pH suits the cosmetically active group, R.

Many of the embodiments of the present invention compπse a silicone composition which includes at least one polysiloxane or silicone resm, at least one linker, and at least one molecular hook. For example, said silicone composition typically imparts improved hair care benefits when added to hair care compositions.

The at least one linker is bound to both a molecular hook and to an atom of a polysiloxane or silicone resm. Preferably the at least one linker is bound to a polysiloxane or silicone resm through a silicon, carbon, oxygen, nitrogen, or sulfur atom, and most preferably to a silicon atom. When more than one linker is present, it is also contemplated that linkers may be bound to a polysiloxane or silicone resm through more than one type of atom, for example through both silicon and carbon atoms.

Therefore, in one embodiment the present invention compnses at least one polysiloxane or silicone resm having the formula:

MaM' DcD'dTeT^'fQg

where the subscπpts a, c, d, e, f and g are zero or a positive integer, subject to the limitation that the sum of the subscnpts b, d and f is one or greater; where M has the formula:

M' has the formula:

D has the formula: R³ Sι0₂/2,

D has the formula.

(Z-X)R⁴Sι0₂/2

T has the formula:

R5SI0_3/2,

T^' has the formula:

(Z-X)SιO₃/2,

and Q has the formula S1O4/2, where each R*, R^, R3_; R4₅ R5 _1S independently at each occurrence a hydrogen atom, C] ₂₂ alkyl, C,_ ₂ alkoxy, C_{2 22} alkenyl, Qs- aryl, and C_{6 22} alkyl-substituted aryl, and C₆.₂₂ aralkyl which groups may be halogenated, for example, flounnated to contain fluorocarbons such as Cι_ ₂ fluoroalkyl; Z, independently at each occurrence, represents the molecular hook; and X, independently at each occurrence, represents the linker. The term "alkyl" as used in various embodiments of the present invention is intended to designate both normal alkyl, branched alkyl, aralkyl, and cycloalkyl radicals. Normal and branched alkyl radicals are preferably those containing from 1 to about 12 carbon atoms, and include as illustrative non-hmiting examples methyl, ethyl, propyl, isopropyl, butyl, tertiary- butyl, pentyl, neopentyl, and hexyl. Cycloalkyl radicals represented are preferably those contaimng from 4 to about 12 nng carbon atoms. Some illustrative non-lmutmg examples of these cycloalkyl radicals include cyclobutyl, cyclopentyl, cyclohexyl, mefhylcyclohexyl, and cycloheptyl. Preferred aralkyl radicals are those containing from 7 to about 14 carbon atoms; these include, but are not limited to, benzyl, phenylbutyl, phenylpropyl, and phenylethyl. Aryl radicals used in the vanous embodiments of the present invention are preferably those containing from 6 to 14 nng carbon atoms. Some illustrative non-hmitmg examples of these aryl radicals include phenyl, biphenyl, and naphthyl. An illustrative non-limiting example of a halogenated moiety suitable for R^ groups is tnfluoropropyl.

The polysiloxanes or silicone resms of the present invention are typically prepared by the hydrosilylation of an organohydrogen silicone having the formula

where the subscnpts a, c, d, e, f and g are zero or a positive integer, subject to the limitation that the sum of the subscnpts b, d and f is one or greater, where M has the formula

Rl₃Sι0_1/2,

M^ has the formula-

R²3-hH_hSιOι/₂,

D has the formula

D" has the formula:

H₂.₁R⁴ ₁Sι0₂/2

T has the formula:

R5SI0_3/2,

T∑ϊ has the formula:

HSι0_3/2;

and Q has the formula S1O4/2, where each R*, R^, R³, R⁴, R-> is independently as defined above.

Hydrosilylation is typically accomplished m the presence of a suitable hydrosilylation catalyst. The catalyst preferred for use with these compositions are descnbed m U.S. Pat. Nos 3,715,334; 3,775,452; and 3,814,730 to Karstedt. Additional background concerning the art may be found at J. L. Spier, "Homogeneous Catalysis of Hydrosilation by Transition Metals, m Advances in Organometallic Chemistry, volume 17, pages 407 through 447, F. G. A. Stone and R West editors, published by the Academic Press (New York, 1979). Persons skilled in the art can easily determine an effective amount of platinum catalyst. Generally, an effective amount ranges from about 0.1 to 50 parts per million of the total organopolysiloxane composition.

The organohydrogen silicone compounds that are the precursors to the compounds of the present invention may be prepared by the process disclosed in U.S. Pat. No. 5,698,654 herewith specifically incoφorated by reference. The '654 patent discloses a sequential catalysis of the ring opening polymenzation of cyclic organosiloxanes using a base catalyst that can be neutralized by a subsequent redistnbution and condensation catalyst such as a Lewis acid catalyst, preferably a phosphonitnhc compound, that permits the rapid synthesis of functionahzed and poly- functionahzed silicone copolymers.

It is to be noted that as pure compounds the subscnpts descnbmg the organohydrogen siloxane precursor and the hydrosilylation adduct of the present invention are integers as required by the vanous rules of chemical stoichiometry. As mixtures of compounds that are descnbed by these formulas the subscnpts will assume non-mtegral values, for the mixtures. The restπctions on the subscnpts heretofore descnbed for the stoichiometnc subscnpts of these compounds are for the pure compounds, not the mixtures.

In specific embodiments of the present invention, the silicone composition typically compnses at least one compound of the following formulas, (I), (IT), (ILL), (X), (XI), and

where each R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R^{1 1}, R¹², R¹³, R¹⁴, Rl5, Rl6, _RH _R18_; Rl9, _R20_{; R}21_{; R}22_{; R}23, _R24_{; R}25_{, R}26, _R27, _R28, _R29, _R30_{5 R}31, _R32_{> R}33, _R34 _R35, _and

R³^ is independently at each occurrence a hydrogen atom, C_1-22 alkyl, Cj.₂₂ alkoxy, C .₂₂ alkenyl, C₆.₁₄ aryl, and C₆- ₂ alkyl-substituted aryl, and C₆.₂₂ aralkyl which groups may be halogenated, for example, flourinated to contain fluorocarbons; Z, independently at each occurrence, represents a molecular hook; and X, independently at each occurrence, represents a linker; wherein "m" in each formula has a value in a range between about 0 and about 13,000, preferably about 0 and about 1000, more preferably between about 1 and about 250, still more preferably between about 5 and about 150, even more preferably between about 10 and about 100, and most preferably between about 20 and about 50; "n" in each formula has a value in a range between about 0 and about 13,000, more preferably between about 0 and about 50, more preferably between about 1 and about 20, still more preferably between about 2 and about 10, and most preferably between about 2 and about 5; "m+n" in each formula has a value in a range between about 1 and about 13,000, preferably between about 3 and about 70, more preferably between about 5 to about 50, and most preferably between about 15 and about 50; "q" has a value of at least one and "p+q" has a value of at least 3, preferably in the range of 3-20, more preferably in the range of 3-10, and most preferably in the range of 3-6. The polysiloxane or silicone resin typically has a molecular weight ranging from about 100 to about 1,000,000, preferably from about 250 to about 50,000, more preferably from about 500 to about 25,000, and most preferably from about 500 to about 7,000. The at least one polysiloxane or silicone resin typically has a viscosity in a range between about 20 centipoise and about 2,500,000 centipoise (about 0.02 to about 2500 Pas). The number of X-Z moieties on a polysiloxane or silicone resin in the composition is at least one Ln preferred embodiments the average number of X-Z moieties on a polysiloxane or silicone resin is between about 1 and about 100. more preferably between about 1 and about 20, still more preferably between about 1 and about 6, and most preferably between about 3 and about 6.

Ln one embodiment of the present invention a polysiloxane- or silicone resm-contammg composition compnses a preponderance of a specific linear, branched, cross-linked, or cyclic polysiloxane or silicone resin. In other embodiments a polysiloxane- or silicone resm-contammg composition compnses a mixture of polysiloxanes and/or silicone resins which may include linear, branched, cross-lmked, and cyclic species. Also, suitable compositions may compπse one or more polysiloxanes and/or silicone resms which may contain adventitious amounts of other species, for example ansmg duπng the synthesis process for said polysiloxanes and/or silicone resms, for example at a level of about 0.0001 wt.% to about 5 wt.% based on total sihcon- contaming species. In illustrative examples suitable compositions may contain adventitious amounts of D₄, or species containing Si-H, Si-OH, and/or Si-O-alkyl bonds.

The molecular hook may be a heterocyclic pyndinium compound (TV), a heterocyclic tnazmium (V), or a heterocyclic pynmidimum compound (VI) :

wherem Y represents optional substituents on the heterocyclic nng or nng system, X represents the linker, Q^" represents a countenon, and A is defined below.

Optional substituents, Y, which can be present on the heterocyclic nng or nng system can be selected from hydrogen or electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between -1 0 and +1 5 compnsing carbon-lmked groups of the classes defined as A¹, A², A³, and A⁴, S-lmked groups including SA¹, SCN, SO-.A¹, S0₃A\ SSA¹, SOA¹, S0₂NA'A², SNA¹ A², S(NA')A², SA'(NA²), SONA'A², O-lmked groups including OA¹, OCN, ONA^², N-lmked groups including NA'A², NAΑ²A³⁺, NA'OA², NA'SA², NCO, NCS, N0₂, N=NA\ N=NOA', NA'CN, N=C=NA*, NA'NA²A³, NA¹NA²NA³A⁴, NA¹N=NA², other miscellaneous groups including CONA'₂, CONA'COA², C(=NA^I)NA¹A², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of the optional substituents via a nng system; Hal is fluonne, chlonne, bromine, or iodine.

A, A¹, A², A³, and A⁴ each represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following, a straight, branched or mono- or polycychc aliphatic, mono- or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0 to 15 heteroatoms, especially oxygen (O), nitrogen (N), sulfur (S), phosphorus (P), silicon (Si) and can incoφorate one or more substituents including, but not limited to, poly or perfluoro substitution.

The counteπon, Q^", can include hahdes, borates, phosphates, tosylates, mesylates, tnflates, and other counteπons known to those skilled m the art.

The linker compnses a Cι-C₅₀ alkyl, aryl, or alkylaryl group, or Cι-C₅₀ heteroaryl group containing one or more heteroatoms, and is optionally functionahzed. Optional functionalization on the linker includes ketones, alkoxys, esters, amides, trifluoromethyl, halogens, mtnles and other polar functional groups known to those skilled m the art. The linker is typically denved from a linker precursor which compnses a linker bound to a leaving group (L) Illustrative leaving groups include hahdes such as chlonde, bromide and iodide, tosylate, mesylate, phosphate; cyclic leaving groups (that is, those m which the leaving group remains bound in the linker) such as epoxy or other cyclic leaving group containing at least one heteroatom; and other leaving groups known to those skilled in the art Preferred leaving groups are bromide and iodide, with iodide being particularly preferred

In synthesis, the leaving group is replaced by a molecular hook, so that the linker becomes bound to a molecular hook In one embodiment the at least one linker precursor may be combined with the at least molecular hook before combining with a polysiloxane or silicone resm In a particularly preferred embodiment the at least one linker precursor may be combined with a polysiloxane or silicone resin before combining with the at least molecular hook Typically, the linker precursor has the formula (VII)

(VII) -D-Ar(Y)_π - CH₂-L

wherein D compnses a group bound to a polysiloxane or a silicone resm, "Ar" is an aromatic or heteroaromatic group, optionally substituted with one or more substituents, "Y" is a substituent, "L" is as defined above; and "n" has a value between zero and the number of free valence sites on the aromatic or heteroaromatic ring Non-hmiting examples of suitable aromatic and heteroaromatic groups in linkers include phenyl, btphenyl, toluyl, naphthyl, pyπdyl, qumolyl, tπazmyl, pyπmidyl, pyndazmyl, furyl, furoyl, and thienyl. Illustrative examples of substituents (Y) which may be bound to said aromatic or heteroaromatic group include Ci ₂₂ straight chain, branched, cycloahphatic, or aralkyl, C^u aryl, fluoro, chloro, bromo, lodo, nitro, nitroso, nitπle, trifluoromethyl, tπfluoropropyl, alkyloxycarbonyl, alkylcarbonyl, alkylamido, alkyl ether, aryl ether, and similar electron-withdrawing, electron-donating, and electron-neutral groups The "D" group may compnse a straight chain, branched, cycloahphatic, or aralkyl group which optionally may contain a functional group, said functional group being bound to D in a pendent position or separating D from the aromatic or heteroaromatic group, or separating D from a polysiloxane or a silicone resm, or m more than one of these positions. Illustrative examples of D groups include Ci ₂₂ alkyl and preferably C_{2 3} alkyl Illustrative examples of functional groups which may be present with D include carbonyl, alkylcarbonyl, oxycarbonyl, alkyloxycarbonyl, nitπle, amido, alkylamido, tπfluoromethyl, and halogen, such as chloro, bromo, and/or fluoro. Preferred examples of linkers are shown m formulas (VLLI) and (LX) :

Sihcone-containing compositions compnsing at least one polysiloxane or silicone resin, at least one linker, and at least one molecular hook typically impart cosmetic and other benefits m applications such as hair care (for example durable hair care benefit), textile care, cosmetics, oral care, and animal care.

In order that those skilled m the art will be better able to practice the invention, the following examples are given by way of illustration and not by way of limitation.

CHARACTERISTICS

The protected thiol compounds of the present invention, when applied to a ammo acid based substrate, have improved uptake levels and reduced levels of fade or removal. That is the thiol functional groups demonstrate improved attachment of the functional group, R, to the amino acid based substrate and longer lasting attachment than alternative reactive technologies. These benefits are demonstrated without requinng addition steps of reducing or oxidizing the substrate which typically are required in the art to achieve durable cosmetic benefits.

Reduction as defined herein compnses chemical compositions and treatments that induce the nucleophihc cleavage of disulfide bonds m keratm substrates resulting in the formation of free thiol groups in the form of cysteinyl ammo acid residues. Reduction is employed m several commercial products and processes including the permanent-waving of human hair, human hair straightening, human hair depilation, and m the dyeing of wool with fiber reactive dyes. Several compounds and processes known to induce keratm reduction include (1) low molecular weight thiols such as thioglycohc acid, thiolactic acid, cysteine, thioglycerol, thioglycohc hydrazide, thioglycolamide, and glycerol monothioglycolate, (u) sulfides such as salts of hydrogen sulfide, (m) high temperature and alkali wherem the keratm is heated to around 100°C or above by a heating source or steam and wherein the keratm can be contacted with an alkaline solution, (IV) cyanide such as the salts of hydrogen cyanide, (v) phosphines such as tπhydroxymethyl phosphine or its precursor, tetrahydroxymethyl phosphonium chloride, (vi) other miscellaneous reducing agents such as borohydnde, dithiomte, hydrosulfite, and sulfoxylate and (vn) combinations thereof. Reduction as defined herein generally refers to the above processes and compositions which reduce greater than 10% of the disulfide bonds in the keratmaceous substrate The relative quantities of reduced versus unreduced keratin fiber depend on the type of reducing agent, its concentration (or degree of application in the case of heat), the solution-to-hair ratio, pH of the reaction medium, time of reaction, fiber diameter, and the condition of the hair A more detailed discussion on disulfide reduction can be found in the article by Gershon et al (Gershon, S. D.; Goldberg, M. A.; Rieger, M. In Cosmetics Science and Technology, Sagarin. E , eds., pp. 583-627 Interscience, New York (1963)).

Oxidation as defined herein compnses chemical compositions and treatments that induce the oxidative cleavage of disulfide bonds in keratin substrates resulting in the formation of sulfonic acid groups in the form of cysteic acid amino acid residues. Oxidation is employed m several commercial products and processes including the bleaching of human hair, permanent dyeing of human hair with oxidation dyes, and in the dyeing of wool with fiber reactive dyes. Hydrogen peroxide is the pπnciple oxidizing agent used in most oxidizing compositions and is delivered liberally to the substrate as a 3 to 12% solution which may be alkaline. Persulfates, in the form of their sodium potassium and ammonium salts, may also be used to be mixed with the hydrogen peroxide just before use. Other ingredients that may be additionally included in the composition include sodium percarbonate, sodium perborate, magnesium perborate, magnesium dioxide and banum bmoxide. Oxidation as defined herein generally refers to the above processes and compositions which degrade greater than 10% of the disulfide bonds in the keratmaceous substrate. A more detailed discussion on disulfide oxidation can be found in the articles by Zahn and Robbms (Zahn, H. J. Soc. Cosmet. Chem. 17:687 (1966); Rabbins, C; Kelly, C. J. Soc. Cosmet. Chem. 20:555 (1969)).

Both reduction and oxidation of ammo acid based substrates lead to irreparable damage to the substrate by virtue of their destructive chemical reactions. For instance, both reduction and oxidation result in disulfide bond cleavage which has been shown to significantly reduce the wet tensile properties of human hair through 30% extension (Clarence Robbms book: Chemical and Physical Behaviour of Human Hair). Also, reduced hair has been shown to be less πgid in the wet state than unreduced hair (Bogaty, H. J. Soc. Cosmet. Chem. 18:575 (1967)) and the wet bending stiffness and wet stretching stiffness were demonstrated to decrease on oxidized hair (Robbms Book) Furthermore, reduced hair has been shown to exhibit increased fπctional resistance (Schwartz, A.; Knowles, D. J. Soc. Cosmet. Chem. 14:455 (1963)) which is evidence of imparted damage to the hair These demonstrated destructive chemical interactions with keratin have been shown to translate into keratm that is drier, more brittle to the touch, more porous, weaker and which tangles more easily (The Science of Hair Care, by Charles Zviak)

PROCESSES FOR PREPARING THE PROTECTED THIOL COMPOUNDS

The compounds of the invention can be prepared by any of a number of procedures known to those skilled in the art. Several nonlimiting examples are descnbed herein below.

HETEROCYCLIC PROTECTING GROUPS

Alkylthio substituted pyπdmes can be prepared by reaction of halopyπdmes with a variety of thiols in the form of metal salts [Takahashi, Saikachi, Akai, J Pharm Soc Japan, 1943, 63, 153, Adams, Ferreti, J Am Chem Soc , 1959, 81, 4927]. Another method of preparation involves alkylation of pyπdmethiols [Marckwald, Klemm, Trabert, Ber., 1900, B33, 1156; Forrest, Walker, J. Chem. Soc, 1948, 1939].

Alkylthio substituted pyπmidines can be prepared by alkylation of mercaptopyπmidmes [Southon, Pfeiderer, Chem. Ber., 1978, 111, 982; A. G. Geigy, Chem. Abstr , 1969, 70, 68418] or directly from halogenopynmidmes [Semga, Ichiba, Kanazawa, Nishigaki, J. Heterocyclic Chem , 1982, 30, 610].

Alkylthio substituted pyrazmes can be prepared from halogenopyrazmes and appropπate sodium (or potassium) alkyl thiolate at elevated temperatures [Konakahara, Y. Takagi, Bull Chem. Soc. Japan, 1960, 80, 349]. The alternative method is alkylation of mercaptopyrazines [A. Albert, G.B. Barlm, J. Chem. Soc, 1962, 3129].

Alkylthio substituted pyndazmes can be prepared by treatment of halopyπdazmes with a thiol m the form of its alkali salt or with a thiol in the presence of base [Druey, K. Meier, K Eichenberger, Helv. Chim. Ada, 1954, 37, 121; M. Fujisaka, Y. Neno, H. Shinobara, E. Imoto, Bull Chem. Soc. Japan, 1964, 37, 1107; T. Hone, K. Kmjo, T. Ueda, Chem. Pharm. Bull , 1962, 10, 580]. Alkylation of pyndazmethiones and pyndazmethiols as well as some other methodologies are also published. [M. Tisler and B. Stanovnik "Pyndazines and their Benzo Derivatives", m "Comprehensive Heterocyclic Chemistry", 1984, Pergamon Press, Ltd.; M. Tisler and B. Stanovnik "Sulfur Compounds of Pyndazines", in "The Chemistry of Heterocyclic Compounds", 1973, John Wiley&Sons, Inc.] For the alkylthiol substituted tπazmes and tetrazmes, a comprehensive review on the synthesis of these compounds is found in the literature. [M. Tisler and B. Stanovnik, J.Het. Chem , 1971, 785, Reissert and Grube, Chem Ber., 42, 1909, 3720; Gompper and Schoenafinger, Chem Ber , 1 12, 1979, 1529; Arndt, Eistert, Chem. Ber., 60, 2602, 1927; Grundmann et al, J Org Chem , 23, 1958, 1522; Cπstescu, Panaitescu, Pharmazie, 17, 1962, 209; H. Neunhoeffer, H. Hammann, Tet. Lett., 24, 1983, 1767; J. L. Johnson, B. Whitney, L.M. Leslie, J .Het Chem., 17, 1980, 501; S. C. Fields, M. H. Parker, W. R. Eπckson, J Org. Chem , 1994, 8284.]

The six membered O, N, and/or S containing heterocychcs with C=0, C=S or C=C exocyclic groups can be prepared from halogen denvatives of corresponding heterocycles and thiols. [Tominaga, A. Ushirogochi, Y. Matsuda, J. Het.. Chem., 24, 1987, 1557; Y. Tominaga, et al, Chem Pharm, Bull., 32, 3384, 1981; L. Adelfang, J Org. Chem., 31, 2389, 1966; L. W. Singh, H. Junjappa, Synthesis, 5, 531, 1985; W. D. Rudorf, R. Schawrz, Tet Lett , 28 4267, 1987; B Deb, H. Ila, et al, Synthesis, 10, 893, 1987.]

Alkylthio substituted pyndimum denvatives can be prepared by quaternization of the corresponding pyndine alkyl thioethers and other methods. [Yamada, et al, J. Org. Chem., 42, 2180, 1977; M. Yamada, et al, J. Chem. Soc, Chem. Comm., 179, 1979; T. Sakakibara, Y. Watabe, M. Yamada, R. Sudoh, Bull. Chem. Soc. Jpn, 61, 247, 1988.]

Alkylthio substituted xanthenes can be prepared from thiols and xanthene with a suitable leaving group [K. J. Divakar, C.B. Reese, et. al., J. Chem. Soc, Perkin Trans 1, 1990 (6), 1753]

Alkylthio substituted pyπmidmium denvatives can be prepared by quaternization of the corresponding pynmidme alkylthioethers and other methods. [Deichmeister, Platoshknn, Khim. Geterosicl. Soedin., 1, 1961, 333; Brown, England, J. Chem. Soc. C, 1971, 2507; Ueda, Ohtsuka, Chem. Pharm. Bull, 21, 1973, 1451.]

Alkylthio substituted pyrazmmm denvatives can be prepared by quaternization of the corresponding pynmidme alkyl thioethers and other methods. [Barlm, Benbow, J. Chem. Soc, Perkin Trans. 2, 1975, 1385; Honz, et al, Tetrahedron, 26, 1970, 2305; B. Geutsen et al, Tetrahedron, 1989, 6519; S. Baton, A. Messmer, J. Het. Chem., 1990, 1673.]

Alkylthio substituted furans can be prepared from the corresponding furan thiols and alkyl hahdes. [Gorzynski, D. Rewicki, Liebigs Ann. Chem., 1986, 625; P.G. McDougal, Y-I Oh, Tet Lett., 27, 139, 1986; R. Tanikaga, et al, J. Chem. Soc, Chem. Com., 1106, 1981; Η. Gotthatdt, CM. Weisshuhn, K. Dorhofer, Chem. Ber., I l l, 3336, 1978; R. Adams, A. Ferretti, /. Am. Chem Soc, 81, 4927, 1959; A. Ferretti, G. Tesi, Chem Ind., p. 1987, 1964; L. M. Yagupolskn, N.V. Kondratenko, V.P. Sambur, Synthesis, 721, 1975; B.L. Fennga, et al, Synthesis, 316, 1988; S.P. Tanis, D.B. Head, Tet. Lett., 25, 4451, 1984.] Alkylthio substituted pyrroles can be prepared by S-alkylation of 2- and 3-pyrrolethιols under standard base-catalyzed conditions. [K. Olsen, H.R. Snyder, J Org Chem , 30, 184, 1965, S Apparao, H. Ila, H Junjappa, Synthesis, 65, 1981, M. Cardelhni et al, Synthesis, 1980, 886; A K. Gupta, H. Ila, et al, Synthesis, 141, 1989; S. Gronowitz, R. Kada, J Het Chem , 1041, 1984; M. Colonna, M. Polni, Gazz Chim Ital , 116, 449, 1986, H. Kojima, H. Inoue, et al, Chem. Lett , 1499, 1989; Y. Tominaga, et al, J Het Chem , 26, 477, 1989.]

Alkylthio substituted thiophenes can be prepared by reacting the alkali salts of thiophene thiols with aliphatic halogen compounds. [Thomas, G. Singh, H. Ila, H. Junjappa, Tet. Lett , 30, 3093, 1989; W -D. Rudorf, A. Schierhorn, M Augustm, J Prakt Chem , 321, 1021, 1979; J Cymerman-Craig, J. W. Loder, Org Synth. 667, 1963; J. Cymerman-Craig, J. W. Loder, J Chem Soc, 237, 1954; E.J. Smutny, J Am Chem. Soc , 91, 208, 1969.]

Alkylthio substituted pyrazoles, the 3- and 5- denvatives, can be prepared by the alkylation of the corresponding pyrazolethiones [Michaelis, Lachwitz, Chem. Ber , 1910, 43, 2106; Michaelis, /in., 1908, 283].

Alkylthio substituted isoxazoles can be prepared by alkylatmg the thio group at the 3 position of isoxazoles [A.Thuiller and JNialle, Bull.Soc. Chim. Fr., 1959, 1398; W. D. Rudrorf and M. Augustin, J. Prakt. Chem., 1978, 320, 585; : K. Tomita, S. Sugai and M.Saito, Chem. Pharm. Bull, 1979, 27, 2415; S. Sugai and K. Tomita, Chem. Pharm. Bull, 1980, 28, 552].

Alkylthio substituted isothiazoles can be prepared by alkylatmg both 3- and 5- mercaptoisothiazoles [K. R. H. Wooldridge, Adv. Heterocycl Chem., 1972, 14, 1; B. Torretta, G. Ronsisvalle, E. Bousquet, F. Guerrera and M. A. Siracusa, Gazz. Chim. Ital, 1980, 133; : K. Gewald, W. Radke and U. Hain, J. Prakt. Chem., 1980, 322, 1021].

Alkylthio substituted tnazoles can be prepared from the corresponding thiotnazoles by S- alkylation with vanous alkyl bromides [M.A. Weaver, R.R. Giles, Ger. Pat., 1970, 1,919,045; J. Hemdl, E. Schroeder, H.W. Kelm, Eur. J Med. Chem. - Chim. Ther., 1975, 10, 121.].

Alkylthio substituted 1 ,2,4-oxadιazoles can be prepared from the corresponding halogen oxadiazoles and thiols. [M. Paton, D.G. Hamilton, 7et. Lett., 24, 5141, 1983; D.J. Greig, et al, J Chem. Soc, Perkin Trans., 607, 1987; Sumitomo Chem Ind KK, Japan Patent, 1005072 (J6- 1005072), 86-05143, 1986.]

Alkylthio substituted 1,2,4-thιadιazoles can be prepared via dipotassium cyanodithioimmocabonate followed by alkylation [W. A. Thaler and J. R. McDivitt, J. Org. Chem., 1971, 36, 10; : Badische Anilin und Soda-Fabrik A.-G., Br. Pat. 1 1 16198 (1968), (Chem. Abstr., 1968, 69, 86995)].

Alkylthio substituted pyrazohum denvatives can be prepared by reaction of the corresponding alkylthiopyrazoles with alkyl hahdes. [Michaelis, Justus Lieb Ann Chem , 331, 1904, 230; v. Auwers, Bergmann, Justus Lieb. Ann. Chem., 472, 1929, 310; Michaelis, Justus Lieb Ann Chem., 361, 1908, 270; K. Hartke, X.-P. Popp, Arch Pharm, 1994, 385.]

Alkylthio substituted tnazohum denvatives can be prepared from halogen derivatives of the corresponding tπazoles and lithium thiolates [M. Begtnup, Bull. Soc Chun. Belg , 1988, 573].

Alkylthio substituted azepines can be obtained from the corresponding halogen derivatives [W. Steghch, H. Bauek, B.M. Grosse, R. Leschke, T. Josten, J. Klem, J. Heterocycl. Chem , 1990, 107].

Alkylthio substituted thiepinium denvatives can be prepared from the corresponding thiepms and an alkylation agent [H. Hofmann, A. Molnar, Tetrahedron Lett , 1977, 1985; H. Hofmann, A. Molnar, C. Gottfent, Liebigs Ann. Chem., 1983, 425; H. Hofmann, H. Fisher, M. De Vnes, Z. Naturforsch, Teil B, 1990, 1573].

Synthesis routes for heterocyclic protected thiol compounds are exemplified by the following non-limitmg examples: EXAMPLE 1

Pyrimidinium, 2- [ [3- [ \ [4- f (2-hvdroxy- l-naphthalenvD-azolphenvU sulfo nyll aminol propyl^'thiol-1-methyl-. bromide

3-(4-Acetamιdophenylsulfonamιdo^")propyl bromide

To a stirred solution of N-acetylsulfanilyl chlonde (57.15 g, 0.244 mol) m acetone (500 mL) and H₂0 (187.5 mL) at 0°C was added 3-bromopropylamιne hydrobromide (25.0 g, 0.1 14 mol). When a clear solution was obtained, a solution of sodium hydrogencarbonate (44.15 g, 0.526 mol) in H₂0 (550 mL) was added dropwise, maintaining the internal temperature at 0-5°C. When the addition was completed, the reaction mixture was heated at 50°C for 5 h, then cooled to room temperature and poured into ice H₂0 with stimng. After stimng at 5°C for 4 h, the suspension was filtered and the filter cake was washed with H₂0 and dπed in vacuo to give 34 6 g (90%) An additional reaction was performed to give an additional 63 7 g of similar matenal 3-(4-Amιnophenylsulfonamιdo)propyl bromide

A mixture of 3-(4-acetamιdophenylsulfonamιdo)propyl bromide (34 5 g, 0 103 mol), cone. HCl (43 mL) and EtOH (86 mL) was heated at reflux for 0.5 h, and the suspension was poured into a solution of H₂0 (200 mL) and EtOH (150 mL) The suspension was neutralized with 30% NaHC0₃ (aq) to pH 7-8, then filtered The filter cake was washed with H₂0 and dπed in vacuo to give 27.2 g (90%). An additional reaction was performed to give an additional 48 8 g of similar matenal. 2-Hydroxynaphfhalene, l- 4- [ [3-(bromopropyl)]amιnol-sulfonyl1phenyl]azo1-

A solution of 3-(4-amιnophenylsulfonamιdo)propyl bromide (25.0 g, 0.085 mol) in H₂0 (300 mL) and cone. HCl (35.5 mL, 0 426 mol) was cooled to 5-10°C then a solution of sodium nitrite (6.70 g, 0.094 mol) in H₂0 (50 mL) was added portionwise, maintaining the internal temperature below 10°C. When the addition was completed, the solution was stirred for 5 min at 5-10°C, and then the solution was added in three portions (maintaining the internal temperature below 10°C) to a solution of 2-naphthol (12.3 g, 0.085 mol) and sodium hydroxide (22.2 g, 0.554 mol) in H₂0 (150 mL). Additional sodium hydroxide was added during the addition of the diazonium salt to maintain the pH above pH 7. When the addition was completed, the red-orange suspension was stirred at 5-10°C for 10 mm then allowed to stand at room temperature for 20 h The suspension was acidified with cone HCl (45 mL) (pH <5), stirred for 2 h and filtered The filter cake was triturated with H₂0 (4 x 500 mL), then filtered and dπed m vacuo at 60°C to give 37 1 g (97%). 2(lH)-Pvnmιdιnethιone. 1-methyl-

To a stirred mixture of 1 -methyl-2-thιourea (76.6 g, 0.85 mol) and malonaldehyde bιs(dιmethyl acetal) (126.8 g, 0.77 mol) m EtOH (1.5 L) was added 10M HCl (76.6 mL, 0.77 mol) one portion. The resulting mixture was stirred at 25°C for 18 h, then spm-evaporated m vacuo. The residue was dissolved in H₂0 (1.25 L). The solution was made alkaline by the portionwise addition of K₂C0₃ and extracted with CH₂C1₂ (4 x 500 mL). The combined extracts were dπed over MgS0 and spm-evaporated m vacuo to a solid. The crude product was recrystallized from EtOH (600 mL) then dπed to constant weight in vacuo at room temperature to give 22.9 g (23%) of product; mp 186-188°C (uncorrected). An additional reaction was performed to give a total of 40.7 g.

Pynrmdinium. 2-[[3-r[[4-r(2-hvdroxy-l-naphthaIenyl)azol-phenyl1sulfonyl1ammo]propyl1 thiol -1 -methyl-, bromide A solution of 2-hydroxynaphthalene, l-[4-[[[[3-(bromo- propyl)]amιno]sulfonyl)phenyl]azo]- (22 4 g, 0 05 mol) and 2(lH)-pyπmιdιnethιone, 1-methyl- (6 30 g, 0 05 mol) in N,N-dιmethylformamιde (100 mL) was heated at 80°C for 4 h. The reaction mixture was cooled to room temperature and diluted with Et₂0 (400 mL) to give a gummy red suspension. The solvent was decanted, and the residue was dissolved m MeOH:acetone (1.1, 300 mL) The solution was concentrated to dryness to a foam. The foam was triturated with acetone (2.5 L) for 5 h at room temperature. The resulting suspension was filtered and the filter cake was washed with acetone and dried in vacuo at 45°C to constant weight to give 16.1 g (56%) of solid, mp (uncorrected) 169-172°C The proton NMR spectrum was consistent with the proposed structure. Elemental analysis: C H N S Br

Calc. 50.44 4.21 12.19 11.16 13.91

Obs. 50.27 4.47 12.02 11.13 13.97

EXAMPLE 2

Pyrimidinium, l-methyl-2-[2-f[f[5-(dimethylamino -l-naphthalenyllsulfonyllaminol ethyllthiol-, bromide

Pynmidme, 1 ,2-dιhvdro-l -methyl-2-thιo-

To a stirred mixture of l-methyl-2-thιourea (76.6 g, 0.850 mol) and malonaldehyde bιs(dιmethyl acetal) (126.8 g, 0.7722 mol) in EtOH (1.5 L) was added 10M HCl (76.6 mL, 0.766 mol) m one portion. The resulting mixture was stirred at 25°C for 18 h, then spin-evaporated in vacuo. The residue was dissolved m H₂0 (1.5 L). The solution was made alkaline by the portionwise addition of K₂C0₃ (60 g), then extracted with CH₂C1₂ (3 x 1.0 L). The combined extracts were dπed over MgS0 (20 g) and spm-evaporated m vacuo to give 100.6 g (103 3%) of crude product as a solid. This was combined with 24.5 g of previously obtained material and dissolved in reflux g EtOH (900 mL) The solution was stored at 3°C for 18 h. The resulting precipitate was collected by filtration and dπed to constant weight in vacuo to give 30 0 g (24.0% recovery) of purified product.

Pvπmidmium, 1 -methyl-2-[2-[ [[ [-5 -(dimethylamino)- 1 -naphthalenyll sulfonyl] ammo] ethyl] thiol -, bromide

A stirred mixture of the preceding intermediate (10.0 g, 79.3 mmol) and naphthalenesulfonamide, 5-(dιmethylammo)-N-(2-bromoethyl)- (28.3 g, 79.3 mmol) in 1- propanol (150 mL) was heated at reflux for 2 h. The mixture was spin-evaporated in vacuo to a solid residue. The residue was triturated with acetone (200 mL), then collected by filtration and dπed to constant weight in vacuo at 25°C to give 32.0 g (83.6%) of the target compound, mp 196- 198°C (d) (uncorrected). Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S Br

Calc. 47.20 4.79 11.59 13.27 16.53

Obs. 47.25 4.73 1 1.60 13.19 16.68

EXAMPLE 3

Pyridinium, l-methyl-5-(trifluoromethyl)-2-f2-f[[f5-(dimethylaminoVl-naphthalenyl] sulfonyllaminolethyll-thiol-, bromide

N-Methyl-5-tnfluoromethylpyndone

A stirred mixture of 5-(tπfluoromethyl)-2-pyndinol (34.8 g, 0.213 mmol), potassium carbonate (101 g, 0.730 mol) and lodomethane (48.7 mL, 0.783 mol) in dry acetone (750 mL) in a sealed bottle was heated at 59°C for 7 h then cooled to ambient temperature. The reaction mixture was filtered and concentrated to dryness to give a yellow solid. The crude product was punfied by column chromatography (1 kg silica gel) eluted with hexanes:EtOAc (1 : 1) to give a white solid. The solid was dned in vacuo at room temperature for 2 h to give 34.3 g (90% yield). Additional reactions were performed to give a total of 86.9 g of similar product. 2( lH)-Pyπdιnethιone, l-methyI-5-(tπfluoromethyl)-

A stirred mixture of the preceding intermediate (34.3 g, 0.194 mol) and Lawesson's Reagent (39.2 g, 0.097 mol) m dry toluene (195 mL) was heated at reflux for 10 mm, then the toluene was removed by evaporation. The residue was distilled in vacuo (Kugelrohr apparatus) at 120-140°C/3 mm Hg to give pure product as a yellow solid (36.2 g, 96%). Additional reactions were performed to give a total of 89.9 g of similar matenal.

Pyndimum, l-methyl-5-(tnfluoromethyl)-2-[2-[[[[5-(dιmethylamιno)-l-naphthalenyl] sulfonyl]amιno]ethvH-fhιo]-, bromide.

A stirred mixture of the preceding intermediate (46.7 g, 0.242 mol) and naphfhalenylsulfonamide, 5-(dιmethylammo)-N-(2-bromoethyl)- (86.3 g, 0.242 mol) in dry 1- propanol (270 mL) was refluxed for 4.5 h. The reaction mixture was concentrated to give the crude product as a yellow foam. This foam was dissolved in acetone (450 mL) and slowly added to a stimng solution of hexanesπsopropyl ether (2: 1, 12 L) to give a yellow precipitate. The precipitate was collected by filtration, washed with hexanes (500 mL) and dned in vacuo at 40°C. This solid was reprecipitated twice more in a similar fashion to give 92.4 g (69%) of pure target. An additional reaction was performed to give a total of 119.9 g of the target compound; m.p. 125- 129 degrees C (uncorrected). Proton NMR and LR spectra were consistent with the proposed structure. analysis: C H N S Br

Calc. 45.82 4.21 7.63 11.65 14.52

Calc* 45.87 4.61 7.23 11.03 13.75

Obs. 45.91 4.62 7.01 10.78 14.15

*Calc. for C₂iH₂₃BrF₃N₃0₂S₂ 0.1 ι-Pr₂0 0.2 acetone 0.5 H₂0

EXAMPLE 4

Pyrimidinium, 2-rr3,3,4,4,5,5,6,6,7.7,8,8,9,9.10,10,10-heptadecafluorodecyl)thiol-l-methyl-, iodide

2(lH)-Pvnmιdmethιone. 1 -methyl

To a stirred mixture of 1 -methyl-2-thιourea (76.6 g, 0.85 mol) and malonaldehyde bιs(dιmethyl acetal) (126.8 g, 0.77 mol) m EtOH (1.5 L) was added 10M HCl (76.6 mL, 0.77 mol) in one portion. The resulting mixture was stirred at 25°C for 18 h, then spin-evaporated in vacuo. The residue was dissolved in H2-0 (1.25 L). The solution was made alkaline by the portionwise addition of K₂C0₃ and extracted with CH₂C1₂ (4 x 500 mL). The combined extracts were dπed over MgS0₄ and spm-evaporated in vacuo to a solid. The crude product was recrystalhzed from EtOH (600 mL) then dπed to constant weight in vacuo at room temperature to give 22.9 g (23%) of product; mp 186-188°C (uncorrected). An additional reaction was performed to give a total of 40.7 g.

Pyrimidinium. 2-r(3.3.4.4.5.5.6.6.7.7.8.8.9.9.10.10.10-heptadecafluorodecv' hio1-l-methyl-. iodide

A solution of the preceding intermediate (22.9 g, 0.181 mol) and l-ιodo-lH,lH,2H,2H- perfluorodecane (100.5 g, 0.175 mol) in acetone (1.2 L) was heated at reflux for 20 h, cooled to 15°C and filtered. The filter cake was washed with hexanes (500 mL) and dried m vacuo at room temperature to give 48.6 g (40% yield); mp 196-196.5°C (uncorrected). A second reaction was performed to give 11.1 g(38% yield); mp 206-206.5°C (uncorrected). The proton NMR spectrum was consistent with the proposed structure. Elemental analysis: C H N S

Calc. 25.73 1.44 4.00 4.58 Obs. 25.68 1.47 4.05 4.56

EXAMPLE 5

Benzothiazolium, 2- 1 [2- f [ ^'5-(dimethvIamino)-l -naphthalenyll -sulfo nyll aminol ethyll thiol-3- methyl-, bromide

Naphthalenesulfonamide, 5-(dιmethylamιno)-N-(2-bromo-ethyl)-

A suspension of 5-dιmethylammonaphthalene-l-sulfonyl chlonde (52.5 g, 0.194 mol) and 2-bromoethylamme hydro-bromide (42.3 g, 0.206 mol) in THF (550 mL) was cooled to 2°C. A solution of tnethylamme (40.3 g, 0.398 mol) in THF (230 mL) was added dropwise over a 2 h penod while maintaining the internal temperature below 6°C. After complete addition the mixture was stirred at ambient temperature for 72 h. The mixture was claπfied then concentrated to an orange oil which was chromatographed over silica (2.2 kg) packed and eluted with hexanes- EtOAc (3: 1). Fractions (500 mL) containing the punfied product were combined, clanfied then concentrated to a damp solid. This matenal was triturated in hexanes (250 mL), collected on a filter, washed with hexanes (50 mL) then dned to constant weight in vacuo at room temperature to give 61.7 g (89% yield) of product as off-white crystalline solid.

Benzothiazohum. 2-rr2-r[[5-(dιmethylamιno)-l-naphthalenyllsulfonyl]ammolethyl]thιo1-3- methyl-. bromide

A solution of naphthalenylsulfonamide, 5-(dιmethyl-ammo)-N-(2-bromoethyl)- (15.0 g, 42.0 mmol) and 3-methyl-benzothιazole-2-thιone (11.0 g, 60.7 mmol) m acetone (25 mL) was heated at reflux for 4 days (Note 1). After cooling to 5°C, the mixture was diluted with Et₂0 (150 mL) and suction filtered. The filter cake was washed with Et₂0 (200 mL) and sucked dry to give the crude product. The crude product was dissolved m a mixture of CH₂C1₂ (140 mL) and MeOH (30 mL) then diluted with EtOAc:hexanes (1.2, 750 mL). The suspension was suction filtered and the filter cake was washed with Et₂0 (200 mL), then dπed m vacuo at room temperature for 4 h to give the target compound (9.0 g, 40%) as a yellow solid. An additional reaction was performed to give a total of 22 9 g of target compound, mp(uncorrected) 156-159°C Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S Br

Calc 49.06 4 49 7 80 17 86 14.84

Obs. 49.01 4.33 7.69 17 68 15.02

EXAMPLE 6 lH-Imidazolium, l,3-dimethyl-2-f2-[f[f5-(dimethylaminoVl-naphthaIenyllsulfonyll aminolethyllthio iodide

Naphthalenesulfonamide. 5-(dιmethylamιno)-N-(2-bromo-ethyl)-

A suspension of 5-dιmethylammonaphthalene-l-sulfonyl chlonde (50.0 g, 0.185 mol) and 2-bromoethylamme hydro-bromide (40.4 g, 0.197 mol) in THF (500 mL) was cooled to 2°C A solution of tnethylamme (38.5 g, 0.380 mol) in THF (250 mL) was added dropwise over a 2 h penod while maintaining the internal temperature below 6°C. After complete addition the mixture was stirred at ambient temperature for 17 h. The mixture was clanfied, and the filter cake nnsed with THF to remove all of the product. The combined filtrates were concentrated to an orange oil which was chromatographed over silica (2.2 kg) packed and eluted with hexanes- EtOAc (3: 1). Fractions (500 mL) containing the punfied product were combined, clanfied, then concentrated to a damp solid. This matenal was triturated m hexanes (250 mL), collected on a filter, washed with hexanes (50 mL) then dπed to constant weight in vacuo at 40°C to give 56 9 g (86.1%) yield) of product as an off-white crystalline solid. lH-Imidazole. l-methyl-2-[2-[[[[5-(dιmethylamιno)-l-naphthalenvnsulfonyl]amιno1ethyl] thio]-

A suspension of sodium hydπde (2 1 g of 60%, 52 mmol) in DMF (25 mL) was cooled to 10°C A solution of 2-mercapto-l-methylιmιdazole (6.0 g, 52 mmol) in DMF (50 mL) was added dropwise over a 30 min period while maintaining the internal temperature below 15°C After complete addition, the reaction mixture was stirred at ambient temperature for 1 5 h. A solution of the preceding intermediate (18.7 g, 52.3 mmol) in DMF (75 mL) was added in one portion and the resulting solution was stirred at 50°C for 1.5 h then cooled to ambient temperature. The reaction solution was poured over cold Η₂0 (3 L) then extracted with CH₂C1₂ (1 x 1 L and 1 x 500 mL) The combined extracts were washed with H₂0 (750 mL) and saturated brine (750 mL), dπed over Na₂S0₄, clanfied, then concentrated in vacuo to a green oil This material was combined with similar material from a smaller reaction and passed through a pad of silica (750 g) packed with EtO Ac -hexanes (1: 1) then eluted with 1.1, 6 L; 2:1, 3 L; 3: 1, 4 L and finally EtOAc, 3 L. Fractions containing the punfied product were combined, clanfied then concentrated to a green glass which was tnturated in THF (50 mL). The resulting solid was dned to constant weight in vacuo to give 23.6 g (93% yield) of matenal as a light green solid. lH-Imidazolium, l,3-dιmethyl-2- 2-[[rr5-(dιmethylammo)-l-naphthalenyllsulfonyl]amιno] ethyllthiol-. iodide

A solution of the preceding intermediate (23.6 g, 60.4 mmol), DMF (51 mL) and lodomethane (3.76 mL, 60.4 mmol) was stirred m a flask sealed with a rubber septum for 18 h at ambient temperature. The reaction solution was diluted with Et₂0 (1.5 L) and vigorously stirred for 30 mm. The resulting solid was collected on a filter, washed with Et₂0 (2 x 50 mL) then dried m situ. This matenal was dissolved in CΗ₂C1₂ (300 mL) and MeOH (15 mL), clarified, diluted with EtOAc (300 mL), then concentrated to a thick slurry. The resulting solid was collected on a filter, washed with EtOAc (2 x 75 mL), then dπed to constant weight in vacuo to give 27.0 g (71% yield) of product, mp(uncorrected) 184-186 degrees C. Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S

Calc. 42.86 4.73 10.52 12.04

Obs. 42.89 4.73 10.54 12.20

EXAMPLE 7

Pyrimidinium, l-methyl-2-f[8-f(3,4,5-trihydroxybenzoyl -oxyloctyllthiol-, bromide

8-Bromooctyl gallate

A suspension of gallic acid (23.5 g, 0.138 mol), 8-bromo-l -octanol (90.0 g, 0.430 mol), and cone, sulfuric acid (3.0 mL) was stirred and heated at 120-130°C for 0.5 h, then cooled to 100°C and stirred at 100°C for 1 h. Cooled to room temperature, diluted with EtOAc (300 mL), and washed with H₂0 (2 x 200 mL) and bπne (200 mL). The organic layer was dned (MgS0₄), filtered, and concentrated to give the crude product (111 g). The crude material was purified by column chromatography (2.2 kg silica gel eluted with EtOAc:hexanes (2:3)) to give 33.3 g (67%) as a white pasty solid. 2(lH)-Pyπmιdιnethιone, 1-methyl-

To a stirred mixture of 1 -methyl-2-thιourea (76.6 g, 0.85 mol) and malonaldehyde bιs(dιmethyl acetal) (126.8 g, 0.77 mol) in EtOH (1.5 L) was added 10M HCl (76.6 mL, 0.77 mol) in one portion. The resulting mixture was stirred at 25°C for 18 h, then spm-evaporated in vacuo. The residue was dissolved in H₂0 (1.25 L). The solution was made alkaline by the portionwise addition of K₂C0₃ and extracted with CH₂C1₂ (4 x 500 mL). The combined extracts were dned over MgS0₄ and spm-evaporated in vacuo to a solid. The crude product was recrystalhzed from EtOH (600 mL) then dned to constant weight in vacuo at room temperature to give 22.9 g (23%) of product; mp 186-188°C (uncorrected). An additional reaction was performed to give a total of 40.7 g. Pyπmidinium, l-methyl-2-rr8-r(3.4.5-tnhvdroxybenzoyl)-oxy]octyl]thιo]-, bromide

To a solution of 8-bromooctyl gallate (33.3 g, 0.092 mol) in 1-propanol (170 mL) was added the above intermediate (11.7 g, 0.093 mol), and the resulting suspension was heated at reflux (97°C) for 1.5 h (a solution was obtained at 90°C). The hot solution was cooled to 20°C to give a suspension. The suspension was diluted with EtOAc (1.0 L) and suction filtered. The filter cake was washed with EtOAc (400 mL) and air dned. The crude product (42.4 g of yellow solid) was tnturated m acetone (3.0 L) at room temperature for 20 h. The suspension was suction filtered; the filter cake was washed with acetone (50 mL) and dned to constant weight in vacuo at 35°C to give 25.4 g (57%) as a light yellow solid; mp 141-143°C (dec) (uncorrected). The proton NMR spectrum was consistent with the proposed structure. Elemental analysis: C H N S Br

Calc. 49.28 5.58 5 75 6.58 16.39

Obs. 49.21 5.53 5.79 6.50 16.32

EXAMPLE 8

Pyrimidinium. l-methyl-2-f^'3-f(3.4.5-trihvdroxybenzoyl)-oxy1propyl|thiol-, bromide

3-Bromopropyl gallate

A suspension of gallic acid (40.0 g, 0.235 mol), 3-bromo-l-propanol (100 g, 0.719 mol), and cone, sulfunc acid (3.0 mL) was stirred and heated at 115-120°C until a solution was obtained (10-20 mm), then cooled to 100°C and stirred at 100°C for 3 h. Cooled to room temperature, diluted with EtOAc (500 mL), and washed with H₂0 (250 mL), 20% NaHC0₃ (2 x 250 mL), and bnne (250 mL). The organic layer was dπed (MgS0₄), filtered, and concentrated to give the crude product (137 g). The crude matenal was punfied by column chromatography (2.2 kg silica gel eluted with EtOAc:hexanes (1: 1)) to give 65.1 g (95%)as a cream-colored pasty solid. 2(lH)-Pvnmιdmethιone, 1-methyl-

To a stirred mixture of l-methyl-2-thιourea (573.8 g, 6.365 mol) and malonaldehyde bιs(dιmethylacetal) (949.6 g, 5.783 mol) in EtOΗ (11.3 L) was added 10M ΗC1 (575 mL, 5.75 mol) in one portion. The resulting mixture was stirred at 25°C for 18 h then concentrated m vacuo. The residue was dissolved in Η₂0 (11.1 L) and the solution was made alkaline by portionwise addition of K₂C0₃ (448 g). The alkaline solution was extracted with CH₂C1₂ (3 x 7.2 L) and the combined extracts were dned (MgS0₄), filtered, and concentrated to give the crude product. The crude product was dissolved in refluxmg EtOH (4.0 L) and stored at 3°C for 18 h. The resulting precipitate was collected by suction filtration and dπed to constant weight in vacuo at 40°C to give 94.1 g (12.9%) as a yellow solid. Pynmidinium, l-methyl-2-r 3-[(3,4.5-tnhvdroxybenzoyl)-oxy]propyllthιo]-. bromide

To a solution of 3-bromopropyl gallate (54.9 g, 0 19 mol) in 1-propanol (350 mL) was added the preceding intermediate (23 8 g, 0.19 mol), and the resulting suspension was heated at reflux (97°C) for 0 5 h (a solution was obtained at 90°C, then after a few minutes at reflux a precipitate began to fall out of solution). The hot suspension was suction filtered, and the filter cake was washed with 1-propanol (4 x 75 mL) and dned to constant weight in vacuo at 35°C to give 33.5 g (42%) as a light yellow solid; mp 223-225°C (dec) (uncorrected). The proton NMR spectrum was consistent with the proposed structure. Elemental analysis: C H N S Br

Calc. 43.18 4.11 6.71 7.68 19.15

Obs. 42 91 4.14 6.68 7.63 19.15

EXAMPLE 9

Pyridinium. l-methyl-2-^*(hexadecvDthiol-, bromide

Methyl-2-thιopyndone (1)

A stirred mixture of 1 -methyl -2 -pyπ done (20.0 g, 183 mmol) and Lawesson's Reagent (37.0 g, 91.5 mmol) m dry toluene (100 mL) was heated at reflux for 15 mm. then the toluene was removed by evaporation in vacuo at 60°C. The residue was distilled m vacuo to give crude product; bp, 175-177°C (13 torr). This yellow liquid was dissolved m MeOH (15 mL), and the solution was cooled to 0°C with stimng. The precipitated solid was collected by filtration, πnsed with hexanes (2 x 40 mL) and dned to constant weight m vacuo to give 14.0 g (61%) of matenal suitable for further transformation. One additional reaction was performed to furnish another 27.7 g lot of similarly pure intermediate. Pyπdimum. l-methyl-2-r(hexadecyl^')thιo]-, bromide (2)

A stirred mixture of the preceding intermediate (11.1 g, 88.7 mmol) and 1- bromohexadecane (27.1 g, 88.8 mmol) m 1-PrOH (100 mL) was heated at reflux for 3.5 h then clarified by filtration and stored at 3°C for 18 h The resulting crystalline precipitate was collected by filtration, rinsed with EtOH (3 x 15 mL) followed by Et₂0 (2 x 50 mL), then dπed to constant weight in vacuo at 60°C to give 31 1 g (81%) of purified product One additional reaction was performed to give another 66.7 g lot of purified material. The two lots were thoroughly blended to give a total of 97.8 g of product as a white solid; mp(uncorrected) 111-1 14 degrees C. Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S Br

Calc. 61.37 9.37 3.25 7.45 18.56

Obs. 61.46 9.32 3.23 7.40 18.65

EXAMPLE 10 lH-Imidazolium, l,3-dimethyl-2-(hexadecylthio iodide

Reaction sequence:

To a stirred solution of 2-mercapto-l-methyhmιdazole (36.3 g, 318 mmol) in dry DMF (250 ml ) was added NaH (12.7 g, 60% in mineral oil, 318 mmol) in portions over 0.5 h. The resulting solution was stirred for an additional 1 h, then hexadecyl bromide (lOOg, 97%, 318 mmol) was added m one portion. The reaction mixture was heated for 1 h with stirring at 50°C, then cooled and added to stirred ιce-H₂0 (1.5 L). The resulting biphasic mixture was extracted with hexanes (2 x 500 mL). The combined hexane extracts were dπed over Na₂S0₄ (25 g), then clanfied and treated, m one portion, with Mel (lOOg, 705 mmol). The stirred mixture was heated at reflux for 1.0 h then cooled to room temperature. The precipitated solid was collected by filtration and dissolved in CHC1₃ (1.0 L). The resulting solution was clanfied, diluted with hexanes (1.0 L) then concentrated in vacuo at 40°C to a volume of approximately 1.0 L. The resulting precipitate was collected by filtration and dπed to constant weight in vacuo at 40°C to give 80.9 g (53%o) of purified product; mp, 124-126°C (corrected). Elemental analysis: C H N S I

Calc. 52.49 8.60 5.83 6.67 26.41

Obs. 52.63 8.60 5.75 6.59 26.28 sp² CARBON PROTECTING GROUPS

The sp² protected thiol compounds of the present invention can be prepared by any of a number of procedures known to those skilled m the art.

For example, the thiocarboxyhc acid denvatives can be prepared by reacting acyl chlorides with H₂S or alkylthiols. The carbamothioic acid derivatives can be prepared via hydrolysis of thiocyanates. The dithiocarboxyhc acid derivatives can be prepared by treating carboxylic acids with P₄Sιo and a primary alcohol. The carbonodithioic acid derivatives can be prepared by the addition of alcohols to carbon disulfide in the presence of base to form a salt of the acid and by imparting an alkyl halide to the reaction mixture to form the ester. The carbamodithioic acid derivatives can be prepared by the addition of pπmary or secondary amines to carbon disulfide.

The following non-hmitmg examples illustrate exemplary methods of preparing a few compounds of the invention.

EXAMPLE 11

1-Naphthalenesulfonamide, 5-(dimethylamino)-N-[2-[^'(2-(ethoxy)thioxomethyl1thiol ethyl]-

Naphthalenesulfonamide, 5-(dιmethylamιno -N-(2-bromoethyl)

A suspension of 5-dιmethylammonaphthalene-l-sulfonyl chlonde (50.0 g, 0.185 mol) and 2-bromoethylamιne hydro-bromide (40.4 g, 0.197 mol) m THF (500 mL) was cooled to 2°C. A solution of tnethylamme (38.5 g, 0.380 mol) in THF (250 mL) was added dropwise over a 2 h penod while maintaining the internal temperature below 6°C. After complete addition the mixture was stirred at ambient temperature for 17 h. The mixture was clanfied then concentrated to an orange oil which was chromatographed over silica (2.2 kg) packed and eluted with hexanes- EtOAc (3:1). Fractions (500 mL) containing the punfied product were combined, clarified, then concentrated to a damp solid. This matenal was tnturated m hexanes (250 mL), collected on a filter, washed with hexanes (50 mL) then dπed to constant weight in vacuo at 40°C to give 56 9 g

(86 1% yield) of product as a off-white crystalline solid.

1 -Naphthalenesulfonamide, 5-(dιmethylammo)-N-[2-[ (ethoxy)-thιoxomethyllthιo]ethyl]-

A mixture of the preceding intermediate (43 3 g, 121 mmol) and O-ethylxanthic acid, potassium salt (19 7 g, 123 mmol) in anhydrous acetone (430 mL) was heated at reflux for 18 h The mixture was cooled to ambient temperature, clanfied, and the filtrate was concentrated in vacuo to an oil. This material was chromatographed over silica gel (1 kg) packed and eluted with hexanes-EtOAc (3: 1). Fractions containing the purified product were combined, clarified, then concentrated to a thick slurry which was diluted with hexanes (200 mL). The resulting solid was collected on a filter, rmsed with hexanes (2 x 75 mL), then dπed to constant weight in vacuo to give 19.1 g of product. The mixed fractions from this column were combined, concentrated, then rechromatographed over silica gel (2 0 kg) packed and eluted with hexanes-EtOAc (3 1) Fractions containing the punfied product were combined, clanfied, then concentrated m vacuo to a thick oil. This was dissolved m CH₂C1₂ (50 mL), diluted with hexanes (200 mL), then cold evaporated to a thick slurry. The resulting solid was collected on a filter, washed with hexanes (100 mL), then dπed to constant weight in vacuo to give 18.9 g of product. A second crop of matenal was obtained by cold evaporating the two combined filtrates to give 0.5 g of product (total yield 38.5 g, 82%), mp(uncorrected) 85-86 degrees C. Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S

Calc. 51.23 5.56 7.03 24.13

Obs. 51.19 5.56 6.99 24.14

EXAMPLE 12 S-hexadecyl ethanethioate

Reaction sequence:

O O

I I II

CH₃CC1 + HS(CH₂)ι₅CH₃ *^» CH₃CS(CH₂)i5CH3

A mixture of acetyl chlonde (1.0 L, 1.1. kg, 14 mol) and 1-hexadecanethιol (95%, 168 g, 0.62 mol) was stirred at reflux for 3 h, then volatile components were removed by evaporation in vacuo (60°C, 5 torr). The residue was recrystalhzed from warm (35°C) hexanes (500 mL) by cooling at 4°C for 18 h. The weight in vacuo to give 174.5 g (94%) of punfied product; mp, 29- 31°C (corrected). Elemental analysis: C H S

Calc. 71.93 12.07 10.67;

Found 72.17 12.12 10.84. The NMR (500 MHz) and LR agreed with the proposed structure.

EXAMPLE 13

-y-(4-AminobutvP hexadecanethioate hydrochloride

Reaction sequence:

O o s

II a. N(CH₂)₄Br CH₃CH₂OCS₂ ^" K N(CH₂)₄SCOCH₂CH₃

O 1 o

H₂NNH₂ * H₂0 HCl

HCl * H₂N(CH₂)₄SH

2

O O

II II c. CH₃(CH₂)₁₄CC1 CH₃(CH₂)₁₄CS(CH₂)₄NH₂ * HCl

a. (4-Phthalιmιdobutyl)xanthιc acid. O-ethyl ester (1)

A mixture of N-(4-bromobutyl)phthahmide (138 g, 489 mmol) and O-ethylxanthic acid, potassium salt (97.7 g, 609 mmol) in DMF (400 mL) was stirred for 1 h then blended into stirred ιce-H₂0 (2 kg). The precipitated solid was collected by filtration, air-dπed and doubly recrystallized from boilmg EtOH (2 x 700 mL). The recovered solid was dned to constant weight m vacuo at 50°C to give 114.8 g (73%) of matenal suitable for further transformation. b. 4-Ammo-l-butanethiol hydrochlonde (2)

To a solution of (I) (105.8 g, 327.4 mmol) in CH₃CN (400 mL) was added H₂NNH₂ * H₂0 (47.6 mL, 49.2 g, 980 mmol). The mixture was stirred for 0.5 h at 60°C then evaporated in vacuo at 40°C to a solid residue. This matenal was dissolved in H₂0 (450 mL) and the pH of the solution was adjusted to 2-3 with concentrated HCl. The resulting suspension was stored for 1.0 h at 0°C, then the precipitate was removed by filtration. Additional concentrated HCl (200 mL) was added to the filtrate and the yellow solution was heated at reflux for 6.0 h, dunng which time the evolution of COS gradually slowed to a stop. The resulting solution was evaporated in vacuo at 60°C to a semi-solid residue. This residue was dried by azeotropic distillation with toluene (3 x 100 mL) and then extracted into CH C1₂ (900 mL). Evaporation of the clarified CH₂C1₂ extract yielded 31 4 g (68%) of the hydrochloride salt as a very pale yellow semi-solid suitable for further transformation. 5-(4-Ammobutyl) hexadecanethioate hydrochloride (3)

A solution of (TT) (31.4 g, 222 mmol) and palmitoyl chloride (60.9 g, 222 mmol) in dry CH₃CN (400 mL) was stirred at 70°C for 2.0 h and then at 10°C for 1.0 h. The precipitated solid was collected by filtration and air-dned. This material was recrystallized from boiling EtOH (400 mL) to give a white crystalline solid which was collected by filtration, washed with Et₂0 (3 x 100 mL) and dried to constant weight m vacuo at 60°C to give 52.0 g (62%) of purified product; mp, 138-141°C (corrected). Elemental analysis: C H Cl N S

Calc. 63.20 11.14, 9.33 3.69 8.44;

Found 63.32 11.16 9.22 3.71 8.37. The NMR (500 MHz) and LR agreed with the proposed structure.

EXAMPLE 14

Methanaminium, N-methyl-N-[l-(hexadecv^'thio)ethylidenel-, bromide

S N(CH₃)₂ ⁺ Br^"

I I I I

CH₃CN(CH₃)₂ + CH₃(CH₂)₁₅Br *• CH3(CH₂)₁₅S-C-CH3

1 To a stirnng solution of N,N-dιmethylthιoacetamιde (33.8 g, 0.33 mol) in acetomtπle (300 mL) was added 97% 1-bromohexadecane (103.1 g, 0.33 mol) and tetrahydrofuran (200 mL), to give a complete solution . The mixture was heated at reflux for 72 h. After cooling to 10°C, the suspension was suction filtered, and the filter cake was washed with Et₂0 (500 mL). The white solid was dried in vacuo at room temperature for 6 h to give 68.2 g (51%) of target compound as a white solid; mp 80-92°C (uncorrected). Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S Br

Calc. 58.80 10.36 3.43 7.85 19.56

Obs. 58.56 10.43 3.41 7.76 19.60

sp³ Carbon Protecting Groups The compounds of the invention can be prepared by any of a number of procedures known to those skilled in the art.

For example, the thioether compounds can be prepared by the treatment of a suitable alkyl halide with a thiol. The thioacetal and dithioacetal compounds can be prepared by the treatment of suitable aldehydes and ketones with a thiol. The compounds capable of undergoing heterolytic β-ehmmation can be prepared via nucleophihc addition of a thiol onto a suitable activated olefin in a Michael-type addition reaction.

EXAMPLE 15

1 -NaphthalenesuIfonam.de, 5-(dimethylaminoVN-f2-ff2-(methvI-sulfonv^*)ethyl] thiolethyll-

To a stirred suspension of 2-(methylsulfonyl)ethanethιol (17.5 g, 0.12 mol) and 5- (dimethylammo)-N-(2-bromoethyl)-l-naphthalenesulfonamide (43.8 g, 0.12 mol) m acetone (1 8 L) was added anhydrous potassium carbonate (19.6 g, 0.142 mol) at room temperature under argon. The reaction mixture was refluxed for 1 h, then additional potassium carbonate (58.5 g, 0.42 mol) and acetone (50 mL) were added followed by continued reflux for 1.5 h. The reaction mixture was cooled to room temperature, then poured into stirred water (8 L) and extracted with EtOAc (2 x 4 L). The combined EtOAc extracts were washed with water (1 x 4 L) then washed with bnne (1 x 4 L) and dπed over magnesium sulfate. The clear EtOAc extract was concentrated to give crude product. The crude product was chromatographed on silica gel (2.2 kg) with EtOAc:hexanes 1 :1 (12 L) and 4:1 (8L). Appropπate fractions were combined, filtered and concentrated to give 47.6 g (93.7 % yield) of product as a viscous oil. Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H N S

Calc 49.01 5.81 6.72 23.09

Calc* 49 34 6.01 6.32 21.71

Obs. 49.52 5.98 6 41 21.96

*Calc. for C_I7H₂₄N₂0₄S₃ . 0.3 EtOAc

EXAMPLE 16

Methvl 3-(Hexadecvlthio propanoate

Reaction Sequence:

O O

II

CH₃(CH₂)ι₅SH + CH₂=CHCOCH₃ CH₃(CH₂)₁₅SCH2CH2COCH3

Hexadecyl mercaptan (95%, 180 g, 661 mmol) was added, dropwise over 0.5 h, to a stirred mixture of methyl acrylate (60.0 g, 697 mmol) and benzyltnmethylammonium hydroxide (40 wt.% in methanol, 400 mg, 1.0 mmol). The resulting warm (~60°C) solution was stirred for one additional hour then volatiles were removed m vacuo at 90°C. The resulting oil was recrystallized from warm (~40°C) hexanes (500 ml), cooled to -30°C, collected by filtration and dned to constant weight in vacuo at room temperature to give 222.3 g (98%) of punfied product; mp, 38-39°C (corrected). Elemental analysis: C H S

Calc. 69.71 11.70 9.30;

Found 69.78 11.54 9.26. The Η NMR and LR agree with the proposed structure.

EXAMPLE 17 4-ffHexadecv^*thio methyll-N.N-dimethv^*benzenamine

Reaction Sequence: a 0₇N

+ Fe/NFLjCl

NaHCO

+ (CH₃0)₂S0₂ (CH₃)₂N S(CH₂)₁₅CH₃

THF/H₂0 ~\_)-^CH2

4- [(Hexadec ylthιo)methyl 1 - 1 -nitrobenzene ( \) :

A solution of 4-mtrobenzyl bromide in ethanol (150.0 g, 0.694 mol in 1.5 L) was brought to reflux Separately, a solution of 1 -hexadecanethiol in ethanol (231 mL, 0.691 mol in 1.5 L) was treated with sodium ethoxide in ethanol (258 mL, 0.691 mol of a 21% solution) over ten minutes, stirred at room temperature for 15 minutes, then warmed to dissolve the precipitate. This was then added to the benzyl bromide solution over twenty minutes, stirred at room temperature for two hours, then allowed to sit undisturbed overnight. The crystallized thioether was collected and combined with the product from a 230 mmol run. This light yellow solid was dissolved in CH₂C1₂ (3 L), washed with water (1 L), then dned (Na₂S0₄), filtered, and spm-evaporated to give 324.5 g of I (89.5% yield). The matenal was a single spot by TLC (19:1 hexanes/EtOAc), and was suitable for further transformation. 4-[(Hexadecylthιo)methyl]benzeneamme (2):

Ammonium chlonde (152.9 g, 2.858 mol), 1 (225.0 g, 0.572 mol), water (2.8 L), methanol (3.8 L) were combined and mechanically stirred at 50°C, then powdered iron (95.9 g, 1.715 mol) was added portionwise over ten minutes. The suspension was vigorously stirred at reflux for 2.5 hours, then hot filtered through a cehte pad. The pad was nnsed with water (3 x 700 mL) and CH₂C1₂ (5 x 700 mL). The aqueous layer was extracted with CH₂C1₂ (3 1 L), then concentrated to remove methanol and again extracted with CH₂C1₂ (3 x 500 ml). The combined orga cs were washed with water (2 x 3L), dπed (Na₂S0₄), filtered, and spm-evaporated to give 198.1 g (95.3% yield) of 2 as a pale yellow solid. TLC (7: 1 hexanes/EtOAc) indicated a single spot. This lot was combined with that of a 100 mmol run to give a total of 231 g of 2 (94.3% yield) which was suitable for further transformation. 4-[(Hexadecylthιo methyl1-N,N-dιmethylbenzeneamιne (3V A solution of sodium bicarbonate in water (168 g, 2.0 mol in 1.3 L) was added to a vigorously stirred solution of 2 in THF (181 g, 0.5 mol m 1.5 L), under argon, at OoC. Dimethyl sulfate (165 mL, 1.75 mol) was added dropwise over 30 minutes, and stirring was continued for a total of 20 h. The ice bath was removed after the first hour. The reaction was followed by TLC (9: 1 hexanes/EtOAc), and initially showed mono-methylated material at Rf = 0.56. After 20 h, concentrated NH₄OH (300 mL) was added and stirred for 15 minutes, then EtOAc and bnne (1 L each) were added and the layers were separated. The aqueous portion was saturated with solid NaCl, extracted with EtOAc (5 x 500 mL), and discarded. The combined organics were washed with bnne (500 mL), dned (Na₂S0₄), and spm-evaporated to a yellow oil. A similar reaction was done previously on 137.7 mmol of 2. The combined lots were dissolved in CH₂C1₂, then eluted from a silica gel pad with CH C1₂. The eluent was spin-evaporated to give 160.1 g of 3 as an oil, which was purified by chromatography (1.8 kg Sι0₂ eluted with 39: 1 hexanes/EtOAc) to give 91.1 g of 3. This material was recrystalhzed from ethanol containing 1 % water, then dπed in vacuo at room temperature to give 57.9 g (23.3% yield) of pure 3; m.p. 41-43°C. Elemental analysis: C H N S

Calc. 76.66 11.58 3.57, 8.19; Found 76.37 11.63 3.61 8.43. The Η NMR, ¹³C NMR, and LR agree with the proposed structure.

EXAMPLE 18

1,3,5-Cvcloheptatriene, 7-fhexadecv^'thio)-

Tropyhum tetrafluoroborate (10.0 g, 0.056 mol) was ground and placed m a reaction flask with MeOH (100.0 mL). This suspension was stirred under argon for 10 mm at room temperature, and then n-hexadecanefhiol, (90%) (15.0 g, 0.052 mol) was added over 5 mm. The reaction mixture (suspension) was stirred for 2 h. At this point, TLC showed only a small amount of unreacted thiol. To the reaction mixture was added NaHC0₃ (8 g, 0.095 mol) followed by stimng for 15 min. and filtration through a small pad of silica gel (-20 g) with elution by hexanes (200 mL). The solution was evaporated (bath temp ~30°C) to give an oil which was punfied by column chromatography with silica gel (100 g) elutmg with hexanes to give 17.2 g (95%) as a colorless oil. Additional reactions were performed to give a total of 58.1 g of target compound. Proton NMR and LR spectra were consistent with the proposed structure. Elemental analysis: C H S

Calc. 79.24 11.56 9.20 Obs. 78.63 11.85 9 43

Metal Based Protecting Groups

The metal mercaptides of the present invention can be prepared by a number of methods known to those who are skilled m the art.

R-S-Met-X_n can be made by reactions of the type:

Met(OA')_n+1 + RS^" ► RSMet(OA')_n + OA^{1 "} e.g., for Ti and Zr.

R-S-Met(M)_mX_n can be made by reactions of the type: Met(M)_mX_{n+ 1} + RS^" »► RSMet(M)_mX_n + X_n ^"

Furthermore, metal mercaptides of the present invention can be made via the addition of the cosmetic thiol to a solution of salts of heavy metals. This can be accomplished by adding the thiol to an aqueous, hydroalcoholic or alcoholic solution of a salt of the metal. The formed mercaptides of the heavy metals may then precipitate. The precipitated mercaptide can then be filtered and washed with an aqueous, hydro-alcoholic or alcoholic solution containing some of the thiol to prevent hydrolysis [E. Reid, Organic Chemistry of Bivalent Sulfur, Volume I, 1958].

Non-metal and metalloid based Protecting Groups

Thiol denvatives of non-metals and metalloids can be prepared from their hahdes in the presence of a hydrogen halide acceptor hydrogen halide acceptor or by using a metal thiolate, such as lead, where Et represents an ethyl group, Pb is lead, and the other symbols are as defined above [M. E. Peach, "Thiols as Nucleophiles", m The Chemistry of the Thiol Group, 1974, John Wiley and Sons, pp. 747.]:

E- Hal + RSH + Et₃N >■ E— S- R + Et₃NH⁺ Hal^"

E- Hal + Pb(SR)₂ »- E— S— R + PbHal₂

Energy Sensitive Protecting Groups

I. 2-Nιtrobenzyl denvatives

The 2-nιtrobenzyl denvatives can be prepared by reaction of the corresponding 2- nitrobenzyl hahde with a thiol m the presence of a base:

IL 2-Nιtrobenzyloxycarbonyl Denvatives

The 2-mtrobenzyloxycarbonyl denvatives can be prepared by the reaction of phosgene with the corresponding alcohol, i.e., 2-nιtrobenzyl alcohol, 6-nιtroveratryl alcohol, 2-nιtrobenzhydrol, and 2,2'-dιmtrodιphenylmethanol. The resulting acyl chloride can then be reacted with a thiol to yield the corresponding 2-nιtrobenzyloxycarbonyl derivative:

where Z¹ and Z² are H, or OCH₃ and Z³ is H, C₆H₅ or o-0₂N-C₆H₄.

iπ. Benzyloxycarbonyl Denvatives

The 3,5-dιmethoxybenzyloxycarbonyl group can be introduced by reacting 3,5- dimethoxybenzyl j9-nιtrophenyl carbonate with a thiol:

IV. α.α-Dimethylbenzyloxycarbonyl Denvatives

The α,α-dιmethyl-3,5-dιmethoxybenzyloxycarbonyl compounds can be prepared by the reaction of α,α-dιmethyl-3,5-dιmethoxybenzyloxycarbonyl azide with a thiol:

V 3 -Nitrophenyloxycarbonyl Derivatives

The 3 -nitrophenyloxycarbonyl compound can be prepared by reaction of 3- mtrophenol with phosgene to yield 3 -nitrophenyloxycarbonyl chloride The latter can then be reacted with a thiol ^•

VI Phenacyl Denvatives

The 4-methoxyphenacyl compound can be prepared by reaction of phenacyl bromide with a thiol:

The α-methylphenacyl compound can be prepared by reaction of alpha-methylphenacyl bromide with a thiol:

VII tert-Butyloxycarbonyl Denvatives

The tert-butyloxycarbonyl compound can be prepared by reaction of tert-butyloxycarbonyl chlonde with a thiol:

CH₃ O CH₃ O

I II RSH I II

CH₃— C-O-C-Cl »^► CH₃— C-O-C-S-R

1 1

CH₃ CH₃

EXAMPLES OF PREFERRED MODIFIED COSMETICALLY ACTIVE AGENTS

The following are non-hmitmg examples of preferred cosmetically active functional group, R. and "hook" combinations for use in topical formulas:

EXAMPLE 19

EXAMPLE 20

EXAMPLE 21

EXAMPLE 22

EXAMPLE 23

Modified Silicone

x = 2 to 500

EXAMPLE 24

Modified Silicone

y=l to 100 x = 2 to 500 EXAMPLE 25

Modified Anti-oxidant

EXAMPLE 26

Modified Perfluoro Conditioner

EXAMPLE 27

Modified UV Absorber

EXAMPLE 28

Modified Anti-oxidant

EXAMPLE 29

Modified Conditioner

CH₃(CH2)i5(OCH₂CH2 6S-

Br^"

wherein Linker represents any straight, branched or mono- or polycyclic aliphatic, mono or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms, especially O, N, S, P, Si, and can incorporate one or more substituents including, but not limited to, poly or perfluoro substitution.

These compounds are made by synthesis methods known in the art, including but not limited to those descnbed above and those descnbed m Sokolowska-Gaida, J. and Freeman, H., Dyes and Pigments (1990) Vol. 14, pp. 35-48, European Patent Application EP 0437099 Al Published by Dow Coming Corp. (Inventors: Halloran, D. J., et al.) and the preparation section herein.

EXAMPLE 30

"Terminal" benzylchloride-substituted silicone polymer.

The hydnde terminated silicone polymer HMe Sι-(OSιMe_:)-OSιMeΗ (35 g, 53 56 mmol. Gelest) was weighed into a 250 mL round bottom flask containing a stir bar 2,6-dι-tert-butylphenol (26 mg, 489 ppm by weight) was added followed by 51 ppm platinum in the form of Karstedt^'s catalyst (GE Silicones Product, 10 2% platinum by weight) The pale vellow solution was placed m a 50°C oil bath Vinylbenzylchloπde (16 8 mL, 1 19.2 mmol, Aldrich) w as added slowly dropwise by syπnge with stirring The solution quickly became cloudy yellow and remained that way until about one mmute after the addition was complete. At this time the reaction mixture turned dark brown. The mixture was stirred at 52°C for 1 5 hours after the addition was complete. The brown mixture was then washed with methanol (1/3 by volume) two times to remove excess vinylbenzylchloπde. The product, a cloudy brown oil, was isolated after drying under vacuum m 83 5 % yield (42.89 g, 44 74 mmol). Η NMR (acetone- d_t) 7 33 (pseudo t, J = 8.0 Hz, aryl). 7.23 (pseudo d, J = 8.0 Hz, aryl), 7 13 (pseudo d, J = 8.2 Hz. aryl). 4.66 (s, 4H, CH.C1), 2 70 (m, 2.4H, SιCH CH_Ar), 2.27 (q, J = 7.6 Hz, 0.8H, SιCH(Me)Ar), 1.38 (d, J = 7.6 Hz, 2.4H, SιCH(Me)Ar), 0 94 (m, 2.4H, SιCH_CH_:Ar), 0.12 (s, 54H, SiMe) The aryl resonances integrate to be 8H total. This product is cloudy brown due to the presence of colloidal platinum. Alternatively, we have found that a very pale yellow product, identical by ' H NMR spectroscopy, can be isolated when the material (mixture of hydrosilation isomers) is prepared using the heterogeneous catalyst Pt Λl₂0₃ (5% Pt). Also noteworthy is the fact that with higher molecular weight silicones, it is possible and recommended to use larger amounts of methanol in the washing step. See Scheme 1. Pyndmium-substituted silicone polymer.

Inside a helium filled dry box, 42.89 g (44.74 mmol) of the ''terminal" benzylchloπde- substituted silicone polymer was added to a 250 mL round bottom flask containing a stir bar. To this was added 10 mL acetone (dned over dnente) and 35 mL anhydrous acetomtnle. Sodium iodide (13.45 g, 89.73 mmol, dned under vacuum at 1 10°C) was added slowly as a solid to the amber solution while sodium chlonde quickly precipitated. The Nal addition was followed by 1 - methyl-5-(tπfluoromethyl)-2(lH)-pyndmethιone (17.30 g, 89.55 mmol, prepared by Starks Associates, Buffalo, NY), added piecewise as a solid. The orange mixture was allowed to stir at room temperature for 3 days. Outside the drybox, the mixture was filtered, and the volatile matenals were then removed from the solution under vacuum. The crude product was dissolved in a minimum amount of acetone (about 75 mL) forming a dark orange solution. Pentane (250 mL) was added to precipitate the product which was filtered on a frit and washed with pentane (5 x 50 mL). The product was isolated in 88% yield (59 g) as a yellow powder. Η NMR (acetone- d ): 9.73 (s, 2H, pyH), 8.73 (m, 4H, pyH), 7.56 (pseudo t, J = 8 Hz, phenyl), 7 29 (pseudo d, J = 8Hz, phenyl), 7.20 (pseudo d, J = 8Hz, phenyl), (the three phenyl resonances integrate to 8H total), 5.03 (s, 4H, CH2S), 4.49 (s, 6H, NMe), 2.71 (m, 2.4H, SιCH2CH2Ar), 2.29 (q, J = 7.4 Hz, 0.8H, SiCH(Me)Ar), 1.39 (d, J = 7.4 Hz, 2.4H. SιCH(Me)Ar), 0.94 (m, 2.4H, SιCH2CH2Ar), 0.12 (s, 54H, SiMe). See Scheme 1.

88.3% yield + product of α- yellow powder hydrosilation

EXAMPLE 31

"On-chain" benzylchloride-substituted silicone polymer.

The "on-chain" hydride silicone polymer Me₃Si-(OSiMe₂)_2r(OSiHMe)₃-OSiMe_:. (200 g, 102.0 mmol, GE Silicones Product) was weighed into a 250 mL round bottom flask containing a stir bar. To this was first added 2,6-di-tert-butylphenol (128 mg, 504 ppm by weight) and then 150 ppm platinum in the form of the heterogeneous catalyst Pt/Al₂0₃ (5% Pt by weight). The pale yellow solution was placed in a 50°C oil bath and vinylbenzylchloride (50.1 mL, 355.3 mmol, Aldrich) was added by syringe with stirring. The mixture was stirred at 60°C for 4 days. The dark yellow-green reaction mixture was then washed with methanol (1/2 by volume) three times to remove excess vinylbenzylchloride. The product, a clear yellow oil, was isolated in 79.0 % yield after drying under vacuum (194.99 g, 80.64 mmol). Η NMR (acetone- d_ή): 7.33 (pseudo t, J = 7.8 Hz, 6 H, aryl), 7.21 (m, 6 H, aryl). 4 65 (s, 6.0 H, C H C1), 2.73 (m, 4H, SiC ILCI LAr), 2 23 (m, IH, SιCH(Me)Ar), 1.40 (m, 3H. SιCH(Me)Ar), 0.93 (m, 4H, SiC- l_.CH_.Ar), 0.12 (s, 154H, SiMe). The aryl resonances integrate to be 12H total. The final product showed some solubility m methanol so smaller amounts may be recommended m the washing step Significantly lower reaction times (ca 1-2 hours) are needed when the heterogeneous catalyst is replaced with Karstedt' s catalyst, particularly for on-chain substituted hydndes. or when the described reaction is heated to a higher temperature See Scheme 2. Pyrimidinium-substituted silicone polymer.

This "on-chain" benzylchlonde-substituted silicone polymer (31.32 g, 12 95 mmol) was added to a 250 mL round bottom flask containing a stir bar mside a helium-filled dry box. To this was added 20 mL acetone (dπed over dnente) and sodium iodide (5.46 g, 36 39 mmol, dned under vacuum at 1 10°C) as a solid. The solution became cloudy and quickly precipitated sodium chloride. Another 10 mL of acetone was added followed by 4 49 g (35.58 mmol) of the 2(1H)- pynmidinethione (prepared by Starks Associates, Buffalo, NY), added piecewise as a solid. The orange mixture was allowed to stir overnight (approximately 16 hrs.) at room temperature. Outside the dry box, the precipitate was removed and the volatile materials evaporated under vacuum. The product was isolated m 97.3% yield (35.43 g) as a waxy, dark orange solid. Η NMR (acetone-d₆): 9.72 (s, 3 H, pyH), 9.39 (m, 3 H, pyH), 8.02 (pseudo t, J = 4.8 Hz, 3 H, pyH), 7 48 (pseudo d, J = 6.7 Hz, 6H, phenyl), 7.22 (m, 6H, phenyl), 4.82 (s, 6.3 H, CH S), 4.34 (s, 9 0 H, NMe), 2.72 (m, 4H, SιCH₂CH₂Ar), 2.20 (q, J = 7.4 Hz, IH, SιCH(Me)Ar), 1.39 (m, 3H, SιCH(Me)Ar), 0.92 (m, 4H, SιCH₂CH₂Ar), 0.12 (s, 154 H, SiMe). Further studies revealed that the reaction with the pynmidme thione can be performed under air with solvent used as received with the same results. See Scheme 2. The distribution of the on-cham substitution is random, not blocked as depicted schematically. However, the invention is not limited to randomly distributed polymer.

S

-Si4

EXA 32-38

Other pyrimidinium-substituted silicone polymers.

A number of other hook-functionalized silicone polymers were prepared. Vinyl benzylchloride hydrosilation reactions were performed as described in both Examples 1 and 2 while the method used to prepare the pyrimidinium-substituted materials was as described in the second part of Example 2. The new materials synthesized are shown as follows:

EXAMPLE 39 Benzylchloride-substituted silicone resin.

The hydnde substituted silicone resm MH₂Q (101 05g, 0.932 mol Si-H) was weighed into a 500 mL round-bottom flask containing a stir bar. 2,6-di-tert-butylphenol (61 0 mg, 529 ppm by weight) was added followed by 37 6 ppm of platinum m the form of Karstedt's catalyst (GE Silicones Product 89023, 10 0% platinum by weight) The mixmre was placed m a 55°C oil bath and vinylbenzylchloπde (14 30 g, 93.7 mmol, Aldnch) was added dropwise over a penod of one hour. At the end of the addition, the solution went from clear yellow to cloudy yellow. The mixture was stirred at 55°C for 17 hours and then at 95°C for four hours to complete the reaction as determined by Η NMR spectroscopy The mixture was transferred to a 500-mL three-necked round-bottom flask which was placed m a hot oil bath. The internal temperamre was raised to 120°C and 1-hexene (150 mL) was added dropwise over the course of about three hours. The mixture was stirred for an additional 16 hours, however, the temperature dropped due to excess 1-hexene and this hindered the reaction. The excess 1-hexene was removed under vacuum. The reaction was set up again, this time with a slower addition of 1- hexene at 120°C. After a total of 3 days of reaction time, which includes the previous removal step, the final product, a cloudy dark brown liquid, was isolated m 94 8% yield (176.18 g) Η NMR (acetone-d,,) 7.32 (m, phenyl), 7 24 (pseudo d, J = 5 5 Hz, phenyl), 7 16 (m, phenyl), 4 65 (s, Ar( II₂Cl), 2.73 (m, SιCH(Me)Ar). 2 03 (s, SιCH(Me)Ar), 1.31 (br m, SiCI LC ILAr and hexvl). 0 88 (br m, hexyl), 0.65 (br m, hexyl), 0 18 (br m, SiCH_.CH_.Ar and hexyl), -0 24 (br s, SiMe) Shorter reaction times are required if the temperature of the reaction with 1-hexene is maintained at 120°C. Pyrimidinium-substituted silicone resin.

The benzylchloπde-functionahzed resm was converted to the pynmidmium substituted material as descnbed in Example 3 1. The product was isolated in 87.8% yield (25.9 g) as a viscous dark orange liquid. Hair care benefits.

In order to measure hair care benefits imparted by the new silicone mateπals, treated hair switches (4 grams) were contacted with formulations containing the pynmidimum-substiiuied silicone polymer described in Example 3 1 which is referred to as the "3Hook Polymer". Following treatment and simulated consumer use, combing forces were measured using a Reed Combing Machine.

The study of combining forces showed that hair switches treated with the hook-substituted silicone polymer consistently exhibited lower combing forces than the controls. The sample which did contain the hook silicone polymer demonstrated combining benefits over the sample which did not contain the hook silicone polymer. Combing benefits are also evident in the samples containing the 3Hook Polymer compared with the analogous samples which contained PDMS (polydimethylsiloxane, 5 centistokes, 5% by weight) as a control

3Hook Polymer:

Overall, use of the 3Hook Polymer m the hair treatment formulation clearly led to wet combing benefits whether or not conditioner was used. Wet combing benefits were found when the hair was treated once and them subjected to four simulated weeks of shampooing. The combing benefit imparted to hair treated only once was just as profound as that found for hair that was treated weekly with the hook silicone polymer. In addition, the benefit imparted to the hair by the 3Hook polymer was durable, lasting through at least 16 shampoos. While typical embodiments have been set forth for the purpose of illustration, the foregoing descriptions should not be deemed to be a limitation on the scope of the invention Accordingly, various modifications, adaptations, and alternatives may occur to one skilled in the art without departing from the spint and scope of the present invention

METHODS OF USLNG THE PROTECTED THIOL COMPOUNDS OF THE PRESENT INVENTION

The method of use of the various protected thiol compounds is dependent on the product form utilized. The use would be as typically used for the product chosen.

The protected thiol compound of the present invention can be used in a vanety of ways m hair care compositions. For example, in the most basic sense the cosmetic actives of the present invention can be applied directly to the hair m a alcohol/solvent/water solution compnsing:

Protected thiol cosmetic active of Examples 1-20. 30, 31 , 39 0.5 to 10%

Hydroalcoholic solvent 0 to 95.00% pH modifier, i.e , NaOH or citric acid pH 3 to 10*

Water Q.S.

* Note, the pH will vary based on the particular "hook" compound of use and can be adjusted either just pnor to treatment with hair or simultaneously with the treatment of hair.

After application, the hair is washed or nnsed to remove excess solvent. The resulting protected thiol cosmetic active will be delivered and bound to the hair permanently, e.g benefit will last beyond 40 to 80 or more shampoos.

A simple non-hmiting dye composition using the protected thiol compounds of the present invention compnses the following composition ranges (depending on what colour is desired): Modified D&C Violet No. 2 of Example 21 0.00% to 3.00%

Modified D&C Red No. 31 of Example 19 0.00% to 3.00%

Modified D&C Yellow No. 6 of Example 20 0.00% to 3.00%

Modified D&C Black No. 9 of Example 18 0.00% to 3.00%

2-propanol 50.00%

Sodium Hydroxide to pH 9- 10

Water Q.S. wherem the total dye concentration is between 1% and 5%. The preparation of this composition and treatment with hair for proof of performance is descnbed as follows: The dyes are added to the water and 2-propanol solution in a jar and stirred until thoroughly dissolved at room temperature. The hair to be treated is submerged into the solution such that the hair weight comprises 10 to 40 wt% of the composition. The sodium hydroxide is then added, a cap is placed on the jar and the jar containing the solution plus hair is shaken for five minutes. The hair is then removed from the ar and nnsed thoroughly.

A simple non-hmitmg conditioning composition using a protected thiol compound of the present invention compnses:

The Modified Silicone of Example 23 5.00%

Methanol 90.00%

NaOH to pH 8-10

Water Q.S.

The preparation of this composition and treatment with hair for proof of performance is descnbed as follows: The modified silicone is added to the methanol m a jar and stirred until thoroughly dissolved at 100°F. The water and NaOH is then added with stirnng until the solution is thoroughly mixed. With a synnge, one gram of the resulting solution is applied per gram of the hair to be treated. The applied solution is then worked through the hair while weanng rubber gloves. The hair is then covered with plastic wrap and let sit for up to two hours. The hair is then nnsed thoroughly.

The protected thiol compounds can be achieved with any of the protected hooks descnbed herein. Of course, the protected thiol compounds of the present inventions can be applied in diffenng matnces and formulas as descnbed previously herein.

The protected thiol compounds may also be added to technologies currently well known in the art to treat substrates such as hair, teeth, finger nails, textiles, and animal fur. Nonlimiting examples of such compositions are descnbed m the references below, each of which is incorporated herein by reference in its entirety:

Shampoos - U.S. Patent No. RE 34,584 (Grote et al.) issued Apπl 12, 1994; U.S. Patent No. 4,345,080 (Bohch) issued August 17, 1982; U.S. Patent No. 4,379,753 (Bohch) issued Apnl 12, 1983; and U.S. Patent No. 4,705,681 (Maes et al.) issued November 10, 1987 Hair conditioners - U.S. Patent No. 4,387,090 (Bohch) issued June 7, 1983; U.S. Patent No. 5,674,478 (Dodd et al.) issued October 7, 1997; and U.S. Patent No. 5,750,122 (Evans et al.) issued May 12, 1998.

Hair styling compositions - U.S. Patent No. 5,166,276 (Hayama et al.) issued November 24, 1992; U.S. Patent No. 5,565,193 (Midha et al.) October 15, 1996; and U.S. Patent No. 5,658,557 (Bohch et al.) issued August 19, 1997. Hair coloring compositions - U.S. Patent No 4,197,865 (Jacquet et al.) issued April 15, 1980, U S. Patent No. 4,125,367 (Bugaut et al.) issued November 14, 1978, U.S. Patent No. 5,114,429 (Jumno et al.) issued May 19,1992, and U.S. Patent No. 5,279,620 (Jumno et al.) issued January 18, 1994.

Mascara compositions - Commonly assigned U.S. Patent Application Serial Nos. 08/951,285 (Alwatarπ et al), filed October 16, 1997, (Attorney's Docket 6345C); 08/757,538 (Bartholomey et al.), filed November 27, 1996 (Attorney's Docket 6397); and 09/121,138 (Alwatarπ et al.), filed July 23, 1998 (Attorney's Docket 5654C2); and m PCT Application Nos. US96/04154, published October 31, 1996; US97/19786, published May 7, 1998; and US97/21890, published June 4, 1998.

Nail polish and nail polish subcoat compositions - U.S. Patent 4,179,304 (Rossomando) issued December 18, 1979, U.S. Patent 5,538,717 (LaPoteπe) issued July 23, 1996, and U.S. Patent 5,639,447 (Patel) issued June 17, 1997, U.S. Patent 5,567,428 (Hughes) issued October 22, 1996. Toothpaste compositions - U.S. Patent 4,254,101(Denny) issued March 3, 1981, and U.S. Patent 4,314,990 (Denny et al.) issued February 9, 1982, and PCT Application No. WO 96/15767 (Unilever PLC) published May 30, 1996. Textile dye and treatment compositions -

Other typical compositions are found m Cosmetic and Toiletry Formulations, 2nd Ed, Flick, E. W., Noyes Publications (N.J.), Harry's Cosmeticologv, 7^th Ed., Harry, R.G., Wilkinson, J.B., and Moore R.J., Chemical Pub. Co. (NY) (1982); and Cosmetics. Science and Technology. 2^nd Ed., Balsam, M.S. and Sagann, E.S., Wiley- nterscience (NY) (1972) (3 volumes).

Other embodiments of the present invention compnse a system compnsing a topical composition containing the protected thiol compound and an activating mechanism. For example the conditioner composition: EXAMPLE 40

Pyπdmium, l-methyl-2-[(hexadecyl)thιo]-, bromide 3.00%

Urea 10.00%

Cocoarmdopropyl Betame 0.80% isopropanol 50.00%

Water Q.S. can be applied simultaneously with a 5% solution of thioglycohc acid. A preferred embodiment is a kit wherem the dye solution and the thioglycohc acid are packaged in separate chambers of a dual chamber package and delivered simultaneously from the package.

Claims

WHAT IS CLAIMED IS:

1 A topical composition for treating amino acid based substrates comprising a protected thiol compound having the formula

R— (S— Pr)_m where R is a mono or multivalent cosmetically active functional group, S is sulfur, Pr is a protecting group and m is an integer between 1 and 100.

2 A topical composition according to Claim 1, wherem the functional group, R, is selected from the group consisting of antimicrobial compounds, UV-absorbmg compounds, skm conditioning agents, hair conditioning agents, hair repair agents, hair styling agents, hair dyes, scalp treatment agents, anti-mflammatory compounds, antioxidants, colonng agents, perfumes, oral care actives, skin moistunzers, pharmaceutical agents, antidandruff agents, insect repellents, moistunzers, humectants, pearlescent and/or opacifymg matenals, fabnc care actives, pet grooming actives, fabnc anti-wnnklmg agents, shπnk-resistant actives, laundry care actives, hard surfaces actives, textile actives, textile dyes, water-proofing agents, cationic polymers, cationic surface modifiers, hydrophobic surface modifiers, anionic surface modifiers, absorbents, antifungal agents, insecticidal agents, textile color guards, nail actives such as enamel and polish, eyelash actives and mascara, antiperspirant and deodorant actives, anti-acne actives, odor control actives, fluorescent actives, bleaching agents, enzymes, antibodies, dispersing aids, emollients, stabilizers, anti-static agents, anti-seborrhea agents, bπghteners, fluorescent dyes, softeners, cross-linkers, and mixtures thereof.

3. A topical composition according to any of the previous claims, wherem the protecting group is selected from the group consisting hetercychc protecting groups, sp² aliphatic trigonal carbon protecting groups, sp³ carbon electrophihc protecting groups, metal based protecting groups, non-metaloid based protecting groups, energy-sensitive protecting groups and mixtures thereof.

4. A topical composition according to any of the previous claims, wherem the protecting group is a heterocyclic protecting group selected from the group consisting of mono- or polyunsaturated or saturated heterocylic nngs, heterocyclic nng systems, fused heterocyclic nng systems, substituted heterocyclic nngs, substituted heterocyclic nng systems, substituted fused heterocyclic nng systems, and mixtures thereof.

5 A topical composition according to any of the previous claims, wherem the heterocyclic protecting group is selected from the group consisting of six membered heterocycles with one, two, three or four heteroatoms, six membered heterocychcs containing O, N, or S with C=0, C=S or C=C exocyclic groups, cationic six membered heterocycles with one or two heteroatoms, five membered heterocycles with one, two, or three heteroatoms, cationic, five membered heterocycles with two or more heteroatoms, seven membered heterocycles, cationic seven membered heterocycles, combinations of heterocycles in a ring system and a fused system both of which may include carbocyhc nngs without heteroatoms, and mixtures thereof.

6. A topical composition according to any of the previous claims, wherein the protected thiol compound is selected from the group consisting of

\

and mixtures thereof, wherein Hal^" is Cl^", Br^", I^" or any suitable negatively charged countenon.

7. A topical composition according to any of the previous claims, wherein the protected thiol compound is selected from the group consistmg of

CH₃

and mixtures thereof.

8 A topical composition according to Claim 3, wherem the protecting group is an sp² aliphatic tngonal carbon group such that the protected thiol compound has the formula selected from the group consisting of

M¹ M¹ M¹

11 1 11 1 _Λ ι 1 "

R— Nu— C— X R— S— C— E±-Q— S R-E— C— S- -o s

M¹ M² II , 11 ,

R -S— C— E— C-X and mixtures thereof wherein M¹, M² are O, S, NA¹, NOA¹, NA'A²⁺, or CA^CA'Y¹; E¹ is O, S, NA¹, CA'A²; or Nu¹ is NHAΑ²⁺, NA'A², OHA¹⁺, or OA¹; and X¹ represents an electron withdrawing or electron donating group with a Hammett sigma para value between -1.0 and +1.5 compnsing C-hnked groups of the classes defined below as A¹, A², A³; S-hnked groups including SA¹, SCN, S0₂A', SO₃A¹, SSA¹, SOA¹, SONA'A², SOaNA'A², SNA¹ A², S(NA^:)A², S(0)(NA¹)A², SA'(NA²); O- hnked groups including OA¹, OOA¹, OCN, ONA'A²; N-hnked groups including NA^!A², NA'A²A³⁺, NC, NA'OA², NVSA², NCO, NCS, N0₂, N=NA\ N=NOA', NA'CN, N=C=NA¹, NA¹NA²A³, NA¹NA²NA³A⁴, NA'N=NA²; other miscellaneous groups including COHal, CON₃, CONA' , CONA'COA², C(=NA' )NA'A\ CHO, CHS, CN, NC, Hal, and derived groups that connect one or more of X¹, X², X³, X⁴, X³ via a ring system.

9. A topical composition according to Claim 8, wherem the sp² aliphatic trigonal carbon protecting group-nucleophile moiety is selected from derivatives of thiocarboxylic acid, carbonodithioic acid, carbonothioic acid, carbamothioic acid, dithiocarboxylic acid, carbonotrithioic acid, carbamodithioic acid, carboximidothioic acid, carbonimidodithioic acid, and carbommidothioic acid, and mixtures thereof.

10. A topical composition according to Claim 9 wherem the protected thiol compound is selected from the group consisting of

- C H C Ho C H C H -NH ⁺ cr

O

R- -CH, -CHo CH₂ NH₃ Cl^*

CH, -CH, -CH, -CH, -NH, Cl^"

and mixtures thereof.

11. A topical composition according to Claim 3, wherein the protecting group is an sp³ carbon electrophihc protecting group such that the nucleophile-protectmg group moiety is selected from the group consisting of monothioacetal groups, monothioketal groups, monothioorthoester groups, monothioorthocarbonate groups, dithioacetal groups, dithioletal groups, dithioorthoester gropus, dithioorthocarbonate groups, tπthioorthoester groups, thiohemiaminal groups, monothioorthoamide groups, dithioorthoamide groups, sp³ carbon groups capable of undergoing heterolytic β-ehmination, and sp³ carbon nng systems, and mixtures thereof.

12. A topical composition according to Claim 11 wherem the protected thiol compound is selected from the group consisting of

H H

-CH, -c- -OCH3 -CH_? -c- -NH,

:0

OCH3 NH₂

and mixtures thereof.

13. A topical composition according to Claim 3, wherem the protecting group is a metal based protectmg group such that the protected thiol compound has the formula selected from the group consistmg of

and mixtures thereof, wherein Met is an alkaline earth metal, transition metal or a representative metal selected from the group consisting of Mg, Ca, Sr, Ba, La, Ti, Zr, V, Cr, Mo, W, Mn, Fe, Co, Rh, Ni, Pd, Pt, Cu, Ag, Au, Zn, In, Sn, and Bi.; where n and m are zero or integers such that 1 + 2m + n equals the valency of Met; X represents independent electron withdrawing, electron neutral or electron donating groups with Hammett sigma para values between -1.0 and +1.5, and M is O, S, NA¹ or CA'A², where A¹ and A² represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or a straight, branched or mono- or poly- cyclic aliphatic, mono or polyunsaturated alkyl, aryl, hetoroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms.

14 A topical composition according to Claim 13 wherem the protected thiol compound is selected from the group consisting of

N(CH₃)₂ o CH₂CH₃

R-S-Ti-N(CH₃)₂ R_s- V-S-R R-S— Sn-CH₂CH₃ I I I

N(CH₃)₂ S-R CH₂CH₃

OCH₂CH₂CH₂CH₃ S-R

S— T1-OCH₂CH₂CH₂CH₃ R— S-Mo-S— R

OCH₂CH₂CH₂CH₃ R— S-Ni-S— R S-R

OCH₂CH₂CH₂CH₃

R- S— Zr- OCH₂CH₂CH₂CH₃ OCH₂CH₂CH₂CH₃ and mixtures thereof.

15. A topical composition according to Claim 3, wherem the protecting group is a non-metal or metaloid based protecting group such that the protected thiol compound has the formula selected from the group consisting of

M_m

and mixtures thereof, wherem E is a representative non-metal or metalloid element selected from the group consisting of B, Al, Si, Ge, N, P, S, Se, Sb, and Te; wherein n and m are zero or integers such that 1 + 2m + n equals the valency of E; X represents independent electron withdrawing, electron neutral or electron donating groups with Hammett sigma para values between -1.0 and +1.5, and M is O, S, NA¹ or CA'A², where A¹ and A² represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or a straight, branched or mono- or poly- cyclic aliphatic, mono or polyunsaturated alkyl, aryl, hetoroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0-15 heteroatoms

16 A topical composition according to Claim 15, wherein the protected thiol compound is selected from the group consisting of

OCH₂CH₃ CH₃ o

R— S— Si-OCH₂CH₃ R— S— Si-CH₃ R— S— S— CH₃

1 1 11

OCH2CH3 CH₃ o

S— R I

R-S— B— S— R O O R— S— Sb-S— R I II I S-R R— S— Ge-O-Ge-S— R S-R

and mixtures thereof.

17 A topical composition according to Claim 3, wherem the protectmg group is an energy sensitive protecting group selected from the group consisting of 2-Nιtrobenzyl groups, 2- Nitrobenzyloxycarbonyl groups, Benzyloxycarbonyl groups,. α,α-Dιmethylbenzyloxycarbonyl groups, 3 -Nitrophenyloxycarbonyl groups, Phenacyl groups, tert-Butyloxycarbonyl groups, and mixtures thereof.

18. A topical composition according to Claim 17, wherem the protecting group is an energy sensitive protecting group selected from the group consisting of 6-mtroveratryloxycarbonyl, dimethyldimethoxybenzyloxycarbonyl, nitrobenzyloxycarbonyl, 5-bromo-7-nιtromdohnyl, O- hydroxy-alpha-methyl-cmnamoyl, 2-oxymethylene anthraqumone, and mixtures thereof.

19. A topical composition according to Claim 17, wherein the protected thiol compound is selected from the group consisting of

and mixtures thereof.

20. A system comprising: a) a topical composition according to any of the previous claims; and b) an activating mechanism.

21 A system according to Claim 20, wherem the activating mechanism is a pH modifier

22 A system according to Claim 20, wherem the activating mechanism is water.

23 A system according to Claim 20, wherein the activating mechanism is an energy source

24. A system according to Claim 20, wherein the activating mechanism is a separate nucleophile.

25 A system according to Claim 20, wherem the activating mechanism is pre-reduced hair.

26. A kit compnsing: a) the system according to Claim 21 ; and b) a package compnsing a first and second chamber; wherem the topical composition is packaged m and delivered out of one chamber and the pH modifier is packaged in and delivered out of the second chamber.

27. A hair care composition compnsmg the topical composition according to any of Claims 1 to 19.

28 A hair care composition according to Claim 27 wherein the protected thiol compound compnses from 0.000001% to 30% of the composition.

29. A hair care composition according to Claim 28, wherein the functional group, R, is selected from the group consistmg of hair conditioners, hair styling agents, dyes and colonng agents, sunscreens, fragrances, antidandruff agents, and mixtures thereof.

30. A textile care composition compnsmg the topical composition according to any of Claims 1 to 19.

31. A textile care composition according to Claim 30, wherem the protected thiol compound compnses from 000001% to 30% of the composition.

32 A textile care composition according to Claim 31, wherein the functional group, R, is selected from the group consisting of dyes and coloring agents, odor control actives, sealants, fragrances, and mixtures thereof

33 A cosmetic composition compnsing the topical composition according to any of Claims 1 to 19

34 A cosmetic composition according to Claim 33, wherem the protected thiol compound comprises from 0.000001% to 30% of the composition.

35 A cosmetic composition according to Claim 34, wherein the functional group, R, is selected from the group consisting of dyes and coloring agents, sealants, resms, varnishes, latex finishes, and mixtures thereof.

36 An oral care composition compnsing the topical composition according to any of Claims 1 to 19

37 An oral care composition according to Claim 36, wherem the protected thiol compound comprises from 0.000001% to 30% of the composition.

38 An oral care composition according to Claim 37, wherem the functional group, R, is selected from the group consisting of anti-canes agents, plaque buffers, anti-plaque agents, agents for alleviating sensitive teeth, matenals that form films and block pores, oral pharmaceutical actives, biomolecules, anti-tartar agents, agents for treating bad breath, anti-calculus agents, and mixtures thereof.

39 An animal care composition compnsing the topical composition according to any of Claims 1 to 19

40 An animal care composition according to Claim 39, wherem the protected thiol compound compnses from 0.000001% to 30% of the composition.

41 An animal care composition according to Claim 40, wherein the functional group, R, is selected from the group consisting of antimicrobial agents, insect repellents, grooming actives, and mixtures thereof

42. A method for attaching a functional group to an amino acid based substrate comprising applying the topical composition according to any of Claims 1 to 19 to the amino acid based substrate.

43 A method according to Claim 42 wherem the acid based substrate is selected from the group consistmg of wool, cotton, animal fur, animal skin, human hair, human skm, human nails, and human teeth.

44. A method for attaching a functional group to human hair compnsing applying the hair care composition according to any of Claims 27 to 29 to human hair in need of such treatment.

45 A method for attaching a functional group to textiles compnsing applying the textile care composition according to any of Claims 30 to 32 to textiles in need of such treatment.

46. A method for attaching a functional group to finger nails or eyelashes compnsmg applying the cosmetic composition according to any of Claims 33 to 35 to nails or eyelashes m need of such treatment.

47 A method for attaching a functional group to teeth compnsing applying the oral care composition according to any of Claims 36 to 38 to teeth m need of such treatment.

48. A method for attaching a functional group to animal fur compnsing applying the animal care composition according to any of Claims 39 to 41 to animal fur in need of such treatment.

49. A topical composition which has the improved combined benefits of stability to air and attachment of the cosmetically active functional group to amino acid substrates upon application without pretreatment of the substrate over previously topical compositions.

50. A hair care composition which results in covalent attachement of cosmetically active functional groups to human hair with significantly less damage occurring on the hair.

51. A process for treating hair comprising the step of applying a safe and effective amount of the hair care composition of any of Claims 27 to 29 to human hair in need of treatment and the step of applying a pH modifier to the hair.

52. The process for treating hair according to Claim 51, wherein the step of applying the hair care composition and the step of applying the pH modifier are performed simultaneously.

53. A textile care composition which results in covalent attachment of cosmetically active functional groups to textiles without severe treatment or pretreatment processes.

54. A silicone composition which comprises at least one polysiloxane or silicone resin, at least one linker, and at least one molecular hook.

55. The composition of claim 54 in which the at least one linker is bound to a polysiloxane or silicone resin through a silicon, carbon, oxygen, nitrogen, or sulfur atom.

56. The composition of claim 55 in which the at least one linker is bound to a polysiloxane or silicone resin through a silicon atom.

57. The composition of claim 54 in which the at least one polysiloxane or silicone resin has the formula:

M_aM'_bD_cD'_dT_eT'fQ_g

where the subscripts a, c, d, e, f and g are zero or a positive integer, subject to the limitation that the sum of the subscripts b, d and f is one or greater; where M has the formula:

Rl₃Si0_1/2,

M^' has the formula:

(Z-X)R² ₂Si0_1/2, D has the formula:

R Si0₂/₂,

D^' has the formula:

(Z-X)R4Si0_2/2

T has the formula:

R⁵Si0_3/2,

T' has the formula:

(Z-X)SiO_{3 2},

and Q has the formula Siθ4/ , where each R*, R², R³, R4_; R5 J_S independently at each occurrence a hydrogen atom, Cι_₂₂ alkyl, Cι.₂₂ alkoxy, C₂.₂₂ alkenyl, C_M aryl, and C₆.₂₂ alkyl- substituted aryl, C₆.₂₂ aralkyl, or Cι_₂₂ fluoroalkyl; each Z, independently at each occurrence, is a molecular hook; and each X, independently at each occurrence, is a linker.

58. The composition of claim 57 in which the average number of X-Z moieties on a polysiloxane or silicone resin is between 1 and 100, preferably between 1 and 6, and more preferably between 3 and 6.

59. The composition of claim 57 in which the at least one polysiloxane or silicone resin comprises at least one compound of the following formulas, (I), (LI), (LIT), (X), (XI), or (XII):

wherein each R^{1 36} is independently at each occurrence a hydrogen atom, C) ₂₂ alkyl, Ci ₂₂ alkoxy, C- 1₂ alkenyl, C_{6 14} aryl, and C_{6 22} alkyl-substituted aryl, C_{6 22} aralkyl, and ₂₂ fluoroalkyl, Z^{1 10}, independently at each occurrence, is a molecular hook, and X^{1 I0}, independently at each occurrence, is a linker, where "m" in each formula has a value in a range between about 0 and about 13.000, "n" m each formula has a value in a range between about 0 and about 13,000, 'm+n" in each formula has a value in a range between about 1 and about 13,000, "q" has a value of at least one and "p+q" has a value of at least 3

60 The composition in accordance with claim 59, wherem a polysiloxane or silicone resin compnses at least one compound of formulas (I), (II), (III), (X), or (XI), wherem R' ³³ is methyl, "m" in each formula has a value m a range between about 1 and about 50, "n" in each formula has a value in a range between about 0 and about 50; and "m+n" in each formula has a value in a range between about 3 and about 70

61 The composition in accordance with claim 59, wherem a polysiloxane or silicone resin compnses at least one compound of formula (XU), where "q" has a value of at least one and "p+q" has a value of 3-6

62 The composition in accordance with claim 57, wherem the linker comprises a -Co alkyl, aryl, or alkylaryl group, or a C₁-C₅₀ heteroaryl group containing one or more heteroatoms

63 The composition m accordance with claim 62, wherem the moiety Z-X is prepared by a process which compnses combining a hook with a linker precursor compnsing a linker and a leaving group.

64 The composition m accordance with claim 62, wherein the leaving group is selected from the group consisting of chlonde, bromide, iodide, tosylate, mesylate, phosphate, and cyclic leaving groups containing at least one heteroatom

65 The composition in accordance with claim 64, wherein the leaving group is iodide

66 The composition in accordance with claim 54, wherem the linker compnses at least one moiety of the formula -D-Ar(Y)_n - CH - wherem "Ar" comprises an aromatic or heteroaromatic group; "Y" is a C| ₂ straight chain, branched, cycloahphatic, or aralkyl group, C_{6 ]4} aryl group; fluoro, chloro, bromo, lodo, nitro, mtroso, nitπle, trifluoromethyl, tnfluoropropyl, alkyloxycarbonyl, alkylcarbonyl. alkylamido, alkyl ether, or aryl ether group; "n" has a value between zero and the number of free valence sites on the aromatic or heteroaromatic nng; "D" compnses a group bound to a polysiloxane or to a silicone resm, said D group comprising a C, ₂₂ straight chain alkyl, branched alkyl, cycloahphatic, or aralkyl group which optionally may contain a functional group, said functional group being bound to D in a pendent position or separating D from the aromatic or heteroaromatic group, or separating D from a polysiloxane or from a silicone resm, or in more than one of these positions, and wherem said functional group compnses carbonyl, alkylcarbonyl, oxycarbonyl, alkyloxycarbonyl, nitnle, amido, alkylamido, trifluoromethyl, chloro, bromo, or fluoro.

67 The composition in accordance with claim 66, wherem the aromatic or heteroaromatic group compnses phenyl, biphenyl, toluyl, naphthyl, pyndyl, qumolyl, tπazinyl, pynmidyl, pyndazmyl, furyl, furoyl, or thienyl.

68. The composition m accordance with claim 66, wherem the linker consists of at least one compound of the formulas (VLH) and (TX) :

69 The composition m accordance w ith claim 57, wherein the molecular hook comprises a heterocyclic pyndimum compound, a heterocyclic tπazinium compound, or a heterocyclic pyπmidinium compound

70 The composition in accordance with claim 69, wherein the molecular hook is at least one member selected from the group consisting of a heterocyclic pyndimum compound (IV), a heterocyclic tnazinium (V), and a heterocyclic pyπmidmium compound (VI)

wherein X is a linker; Y is hydrogen or is selected from electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between -1.0 and +1 5 comprising carbon-lmked groups of the classes defined as A¹, A², A³, and A⁴, S-lmked groups including SA¹, SCN, S0₂A', SO₃A¹, SSA¹, SOA¹, S0₂NAΑ², SNA'A², S(NA')A², SA'(NA²), SONA'A², O- hnked groups including OA¹, OCN, ONA'A², N-lmked groups including NA'A², NAΑ²A³

NA'OA², NA^A², NCO, NCS, N0₂, N=NA' , N=NOA', NA'CN, N=C=NA' , NA'NA²A³,

NA'NA²NA³A⁴, NA'N=NA²; other groups including CONA'₂, CONA'COA², C(=NA')NAΑ², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of the optional substituents via a ring system, Hal is fluonne, chlorine, bromine, or iodine; and wherein A, A¹, A². A³, and A⁴ each represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or polycyclic aliphatic, mono- or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0 to 15 heteroatoms, including oxygen, nitrogen, sulfur, phosphorus, silicon and incorporating one or more substituents including poly or perfluoro substitution; and wherein the countenon, Q^", is selected from the group consisting of hahdes, borates, phosphates, tosylates, mesylates, and tnflates.

71 A hair care composition compnsing the composition of claim 54.

72 A textile care composition compnsing the composition of claim 54.

73 A cosmetic composition compnsmg the composition of claim 54.

74 An oral care composition compnsing the composition of claim 54.

75. An animal care composition compns g the composition of claim 54.

76. A silicone composition compnsing at least one compound of the formula (LI) :

where each R ^' ' is methyl; Z is a pyπmidmium molecular hook of the formula (VI)

wherein Y is hydrogen, A is methyl: Q is iodide; and X is at least one compound of the formulas (VILI) and (TX) :

wherein Z is Z³; and wherein "m has a value in a range between about 15 and about 55; "n" has a value in a range between about 3 and about 6.

77. A silicone composition comprising at least one compound of the formula (I) :

where each R ^* is methyl; Z ^'" are each a pyrimidinium molecular hook of the formula (VI)

wherem Y is hydrogen, A is methyl, Q is iodide, and X is at least one compound of the formulas (VUI) and (DC)

wherein Z is Z^{1 2}, and wherem "m+n" has a value m a range between about 18 and about 61

78 A method for making a silicone composition comprising at least one polysiloxane or silicone resm, at least one linker, and at least one molecular hook, which method compnses combining a linker and a molecular hook with a polysiloxane or silicone resm.

79 The method of claim 78 which compnses combining at least one linker with a polysiloxane or silicone resm and subsequently combining said combination with at least one molecular hook

80 The method of claim 78 in which the at least one linker is bound to a polysiloxane or silicone resm through a silicon, carbon, oxygen, nitrogen, or sulfur atom.

81 The method of claim 80 in which the at least one linker is bound to a polysiloxane or silicone resm through a silicon atom

82. The method of claim 78 in which the at least one polysiloxane or silicone resin compnses at least one compound of the following formulas, (I), (II), (HI), (X), (XI), or (XII):

where each R^1"36 is independently at each occurrence a hydrogen atom, Cι_₂₂ alkyl, C ₂₂ alkoxy, C₂. ₂ alkenyl, C₆.ι₄ aryl, and C₆.₂ alkyl-substi ted aryl, C₆.₂₂ aralkyl, and C,.₂₂ fluoroalkyl; Z^1"10, independently at each occurrence, is a molecular hook; and X ⁰, independently at each occurrence, is a linker; wherein "m" in each formula has a value in a range between about 0 and about 13,000; "n" in each formula has a value in a range between about 0 and about 13,000; "m+n" in each formula has a value in a range between about 1 and about 13,000; "q" has a value of at least one and "p+q" has a value of at least 3.

83. The method of claim 82 in which the average number of X-Z moieties on a polysiloxane or silicone resin is between 1 and 100, preferably between 1 and 6, more preferably between about 3 and about 6.

84. The method of claim 82, wherein the moiety Z-X is prepared by a process which comprises combining a hook with a linker precursor comprising a linker and a leaving group.

85. The method -of claim 84, wherein the leaving group is selected from the group consisting of chloride, bromide, iodide, tosylate, mesylate, phosphate, and cyclic leaving groups containing at least one heteroatom.

86. The method of claim 85, wherein the leaving group is iodide.

87. The method of claim 78, wherein the linker comprises at least one moiety of the formula - D-Ar(Y)_n - CH₂- wherein "Ar" comprises an aromatic or heteroaromatic group; "Y" is a d.₂₂ straight chain, branched, cycloahphatic, or aralkyl group, C_{6 14} aryl group, fluoro, chloro, bromo, lodo, nitro, nitroso, nitnle, tnfluoromethyl, tnfluoropropyl, alkyloxycarbonyl, alkylcarbonyl, alkylamido, alkyl ether, or aryl ether group, "n" has a value between zero and the number of free valence sites on the aromatic or heteroaromatic ring, "D" compnses a group bound to a polysiloxane or to a silicone resin, said D group compnsmg a ₂ straight chain alkyl, branched alkyl, cycloahphatic, or aralkyl group which optionally may contain a functional group, said functional group being bound to D m a pendent position or separating D from the aromatic or heteroaromatic group, or separating D from a polysiloxane or from a silicone resin, or m more than one of these positions, and wherem said functional group compnses carbonyl, alkylcarbonyl, oxycarbonyl, alkyloxycarbonyl, nitnle, amido, alkylamido, tnfluoromethyl, chloro, bromo, or fluoro

88 The method of claim 87, wherem the aromatic or heteroaromatic group compnses phenyl, biphenyl, toluyl, naphthyl, pyπdyl, qumolyl, tnazmyl, pyπmidyl, pyndazmyl, furyl, furoyl, or thienyl.

89 The method of claim 87, wherem the linker consists of at least one compound of the formulas (VIL) and (IX) :

90 The method of claim 82, wherein the molecular hook compnses a heterocyclic pyndimum compound, a heterocyclic tnazinium compound, or a heterocyclic pynrmdinium compound. 91 The method of claim 90, wherein the molecular hook is at least one member selected from the group consisting of a heterocyclic pyndimum compound (IV), a heterocyclic tπazmium (V), and a heterocyclic pyrimidinium compound (VI)

wherem X is a linker; Y is hydrogen or is selected from electron withdrawing, electron neutral, or electron donating groups with Hammett sigma para values between -1.0 and +1 5 comprising carbon-linked groups of the classes defined as A¹, A², A³, and A⁴; S-hnked groups including SA¹, SCN, S0₂A\ SO₃A¹, SSA¹, SOA¹, SO^NA^², SNA¹ A², S(NA^!)A², SA^!(NA²), SONNA²; O- hnked groups including OA¹, OCN, ONA^!A²; N-lmked groups including NA'A², NA'A²A^3~, NA^A², NA'SA², NCO, NCS, N0₂, N=NA^[, N=NOA\ NA'CN, N=C=NA\ NA'NA²A³, NA^!NA²NA³A⁴, NA'N=NA²; other groups including CONA'₂, CONA^OA², C(=NA')NAΑ², CHO, CHS, CN, NC, Hal, and denved groups that connect one or more of the optional substituents via a ring system; Hal is fluonne, chlonne, bromine, or iodine; and wherein A, A¹, A², A³, and A⁴ each represent, independently from one another, a monovalent group which can be the cosmetic active group, R, or H or any of the following: a straight, branched or mono- or polycyclic aliphatic, mono- or polyunsaturated alkyl, aryl, heteroalkyl, heteroaliphatic or heteroolefinic system including 1 to 30 carbon atoms together with 0 to 15 heteroatoms, including oxygen, nitrogen, sulfur, phosphorus, silicon and incorporating one or more substituents including poly or perfluoro substitution; and wherein the counterion, Q^", is selected from the group consisting of halides, borates, phosphates, tosylates, mesylates, and triflates.